Talk:Huntington's disease/Archive 4

Text and/or other creative content from Huntington's disease was copied or moved into Hereditary Disease Foundation with this edit. The former page's history now serves to provide attribution for that content in the latter page, and it must not be deleted as long as the latter page exists.

A quibble concerning the lead

resolved and edited

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Since this article will shortly be on the front page, let me nitpick one sentence in the lead: "Genetic testing can be performed before the onset of symptoms in the relatives of an affected individual, as an antenatal test, and also on test-tube embryos, raising ethical debates." The sentence makes it look like it is the use on test-tube embryos that raises debates, but really it is the pre-onset testing that comes up most. Also I don't understand why the strange word "antenatal" is used -- can't it be "prenatal"? Looie496 (talk) 17:43, 14 February 2010 (UTC)[reply]

Hi Looie! The main page - scary! Agree on all counts - we could also drop the 'in the relatives of an affected individual' as the test can be performed on anyone, just not normally so... think I'll have to have a look at the rest of the article - time pays wanders for spotting obvious improvements ! Lee∴V (talk • contribs) 20:29, 14 February 2010 (UTC)[reply]

Have rewritten and expanded the ethical debates a little. Lee∴V (talk • contribs) 22:20, 17 February 2010 (UTC)[reply]

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last minute changes in history section

no response Dubbin^{u | t | c} 18:15, 13 June 2016 (UTC)[reply]

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Sorry for the last couple of changes just hours before going on the main page, but I received the suggestions from the author of the ref, who stressed they were important for the correct historical context. They seem to check out, there are a couple of others that I have double check before applying at a later date. Lee∴V (talk • contribs) 22:22, 26 February 2010 (UTC)[reply]

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External Review Comments

feedback noted and acted upon Dubbin^{u | t | c} 18:15, 13 June 2016 (UTC)[reply]

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The following comments are from an external reviewer BSW-RMH as part of the new joint Wikipedia talk:WikiProject Medicine/Google Project.

Hello, Huntington's article writers and editors. This article currently has FA status and is a high priority article for the Wikipedia talk:WikiProject Medicine/Google Project. This article is exceptionally well-written, comprehensive, and up-to-date. I hope that I can offer some useful suggestions to enhance it further. Specific suggestions are as follows:

Gene and Protein nomenclature

Done There is a detailed discussion of the correct way to write the gene and protein names for huntingtin on this talk page. The current scientific convention for gene nomenclature is to use the official NCBI ENTREZ Gene ID, all in caps and italicized (HTT). Human protein names are always capitlized and non-italicized (Huntingtin or Htt for short). For a summary of gene and protein scientific nomenclature see: the CDC styleguide (http://www.cdc.gov/ncidod/eid/StyleGuide/scientific_nomenclature.htm). The article would benefit from a thorough check for accuracy and consistency in the protein and gene nomenclature, ex. the huntingtin gene is HTT and the huntingtin gene product is Huntingtin or Htt.

BSW-RMH (talk) 18:18, 13 May 2010 (UTC)[reply]

Thanks for that one. We have never been completely sure on how to do it. Having a reference guide its great. I may add it to the medicine project manual of style.--Garrondo (talk) 06:27, 14 May 2010 (UTC)[reply]

On second reading: I suppose that by the huntington gene product you wanted to say Huntingtin or Htt (protein).--Garrondo (talk) 12:32, 14 May 2010 (UTC)[reply]

Done. I may have missed one (or inadequately changed one) but I think I have changed every HTT to HTT (gene)-although most were correctly spelt already-; HTT and mHTT to Htt and mHtt (protein) and huntingtin to Hutingtin (protein). Bests.--Garrondo (talk) 12:53, 14 May 2010 (UTC)[reply]

Yes it would be good to get this settled ( see section above for current theory ). Alas - can't access the NCBI database right now, but it would seem to contradict the CDC nomenclature guide. From the CDC guide - in genes section: 'Human gene names are all caps, no italics', and then in proteins section: 'Proteins [...] including humans, often have the same name as a gene but are not italicized and always begin with a capital letter.' So I get the Huntingtin/Htt for protein, but should HTT be non-italicized too? Ah and is mHtt correct for the mutant protein? A lot of the confusion comes from various papers and reports on experiments on other organisms, where the nomenclature is different, but the names of the gene/protein the same. This sometimes slips into review articles and references and the confusion spreads!

SThere are some problems with medical terms also ( not conforming to latest accepted usage ), but we defer to the ICD names for consistency, so if we have the same position on genes/proteins that would be good. Lee∴V (talk • contribs) 13:08, 14 May 2010 (UTC)[reply]

You're right. That's not the best reference because it has that internal contradiction. That quoted sentence describes a preference for that particular CDC journal only (Emerging and Infoectious Diseases). Here are other resources making a clarification ie., human genes are italicized but this is not necessary for gene database entries or long lists. Here is a link to the NCBI style guide: [1] stating "Genes are italicized, and proteins are set in roman type (not italic). Use where reasonable. Web pages with long lists of genes in italics would be distracting. In this case, use roman type." Here is a link to the HGNC guidelines:[2] stating, "It is recommended that gene and allele symbols are underlined in manuscript and italicized in print; protein symbols should be represented in standard fonts. Italics need not be used in gene catalogs. To distinguish between mRNA, genomic DNA and cDNA the relevant prefix should be written in parentheses (mRNA)RBP1, (gDNA)RBP1, (cDNA)RBP1." See also, the Wiki article for Gene nomenclature. It is important to note that this convention is for human genes and proteins. Other organisms do not necessarily have the same conventions. BSW-RMH (talk) 16:55, 14 May 2010 (UTC)[reply]

Ah that's better, just a few more bits to go - sorry! re: the name of the gene. From the [guidelines] the first clause states '[Gene names ...] start with a lower case letter unless it is a person's name describing a disease/phenotype or a capitalised abbreviation' . Now I know huntingtin is named in reference to 'Huntington' but it's not exact so makes it non-capitalized, i.e. 'huntingtin'. I remember something from before editing the article so that 'huntingtin' wasn't the first word of a sentence and the capitalization would then lose information! I'm being slightly over-pedantic because I'd like to update WPs guidelines / nomenclature article to be clearer for other editors in future! Lee∴V (talk • contribs) 13:31, 16 May 2010 (UTC)[reply]

On the capitilization issue-that quote is written a bit oddly-you need to look at the examples it gives following that statement: "Names start with a lower case letter unless it is a person's name describing a disease/phenotype or a capitalised abbreviation e.g. AHDS "Allan-Herndon-Dudley syndrome" and ABCA1 "ATP-binding cassette, sub-family A (ABC1), member 1", respectively." So that section actually refers to when you are writing out what the abbreviation of the gene means, don't use capitals to start every word of the abbreviated name unless the word is a person's name. The first letter of the written out name is capitalized no matter what, and all letters of the abbreviation are still capitalized (see examples). BSW-RMH (talk) 15:01, 20 May 2010 (UTC)[reply]

I've double checked and all the terms conform to the above. Lee∴V (talk • contribs) 11:25, 3 June 2010 (UTC)[reply]

Introduction

This section needs supporting citations throughout. I will add citation needed tags the most critical facts requiring support, such as statistics. I found one necessary reference elsewhere, and if time permits I will do more direct fixes. It looks like the necessary references are available later in the article if other editors want to start this process.

I am suprised the terms 'cognitive decline' and 'dementia' are not mentioned earlier in the intro because these are the classic symptoms most people are familiar with in regards to Huntington's. Perhaps they should be emphasized earlier?

BSW-RMH (talk) 18:42, 13 May 2010 (UTC)[reply]

I do not have time now... (I am going to bed), but I only wanted to mention that refs are not usually included in introductions of wikipedia since the lead is only a summary of the article. I have been a major collaborator of this article along with Lee, so I am eager to hear all your comments. Tomorrow more...--Garrondo (talk) 20:05, 13 May 2010 (UTC)[reply]

Gotcha. Even when there are statistics? So far this article is the best I've seen. I'm having a hard time finding anything to suggest as an improvement! BSW-RMH (talk) 20:32, 13 May 2010 (UTC)[reply]

Yeap; it is usually an all or none (I would rather have them, but people do not seem to like the clutter image they produce). There is no problem with the statistics as long as they also appear in the text with their reference. Thanks for the compliment on the article. Me and specially Lee worked really hard to take it to FA (Lee has been working on it for years). We are quite proud, but nevertheless any points for improvement would be most welcome.--Garrondo (talk) 06:25, 14 May 2010 (UTC)[reply]

But that's not to say that convention might be wrong! We did have fully in-lined references before the Featured article review ( or was it one of the GA reviews ). The opinion was that it cluttered the intro, so we moved them all to the end of the lead section. The next point was that this looked wrong ( about 10 refs in a row ), so were removed completely - as Garrondos stated it is taken that if the stat is later in the article with a suitable reference then it can go in the lead. I'm not sure about this convention, only a keen reader will double check that the stats match the ones referenced later in the article, and it is way too easy to add a quick 'misfact' into the lead. On the other hand it gives greater freedom to write the lead in a more readable way and give the gist of whole sections without having to reference each point. We could give the lancet and oxford monographs as two references to cover pretty much most of the article at the end of the lead, but that would probably not be very useful. So we have here a balance of verifiability vs readability, as an outside opinion what would you like to see BSW-RMH? One thought I just had was if this is found to be the current convention that all leads that conform should have a ref/footnote which states 'All facts and statements in this introduction should be able to be found with full references in the main body of this article.' or somethin g like that. Will suggest this at the appropriate place if it sounds good. Lee∴V (talk • contribs) 13:49, 16 May 2010 (UTC)[reply]

Since as you notice has been a back and forth, and it does not seem critical for the outcome of the article (specially since it is quite under vigilance by at least you and me), I think I would rather leave it as it is... There are probably other more important issues in the article and many other articles to work on (Here for example creating a history sub-article, or a greater explanation on genetics). It can be similar to an abstract of an article or a summary of a review, which usually are not referenced. --Garrondo (talk) 17:36, 16 May 2010 (UTC)[reply]

If it follows convention, that's fine. I tend to mentally-tag unreferenced statistics as automatically unreliable, so my personal preference is for statistics to always be referenced because they almost never are presented with all the critical components necessary for interpreting a statistic (sample size, sample inclusion/exclusion criteria, error, sampling method, etc.). That should require one reference per statistic so it shouldn't be cluttered. But as long as the statistic is repeated and referenced in the article, it's technically not critical it be in the intro. BSW-RMH (talk) 15:12, 20 May 2010 (UTC)[reply]

Although it was almost there I haver re-emphasized it in the second sentence.--Garrondo (talk) 16:30, 14 May 2010 (UTC)[reply]

Diagnosis

~~Minor note: "genetic testing can confirm if an individual or embryo carries an expanded copy of the HTT gene that causes the disease"~~

~~This should be worded "expanded copy of the trinucleotide repeat in the HTT gene that causes disease"~~

BSW-RMH (talk) 21:02, 13 May 2010 (UTC)[reply]

Done. This is probably the kind of improvement that is better to be bold and change it yourself than writte it here, since it takes you more time to point it out than fix it and still there is somebody (me in this case :-) who has to come, grasp the comment, be bold and fix it. I know that you have been advised to edit as less as possible, and this is only my opinion...Bests.--Garrondo (talk) 16:16, 14 May 2010 (UTC)[reply]

Differential Diagnosis

~~This is a minor point, but perhaps the lead sentence could perhaps be reworded for clarity. Also, I found 93% for confirmation of intial diagnosis, which could be added to make this more specific.~~

ex. "About 93% of HD diagnoses based on the typical symptoms and a family history of the disease are confirmed by genetic testing to have the expanded trinucleotide repeat that causes HD. Most of the remaining 7% are called HD-like disorders."

Stevanin G, Camuzat A, Holmes SE, Julien C, Sahloul R, Dodé C, et al. CAG/CTG repeat expansions at the Huntington's disease-like 2 locus are rare in Huntington's disease patients. Neurology (2002);58: 965–967)

Partially done: I have left the around 90% since the references are reviews and I would rather have them than the primary article proposed. Nevertheless wording proposed is much better than the one already in the article. Changed.--Garrondo (talk) 10:44, 16 May 2010 (UTC)[reply]

Also, this section touches briefly on HDL disorders. Perhaps a list of the types non-HDL disorders that are sometimes initially misdiagnosed as HD would also be useful. Some of them have Wiki articles that can be linked to. They are well-reviewed in the reference you've already included for this section.

Susanne A Schneider, Ruth H Walker and Kailash P Bhatia. The Huntington's disease-like syndromes: what to consider in patients with a negative Huntington's disease gene test. Nature Clinical Practice Neurology (2007);3,517-525

Done. I have added the examples commented in the article.--Garrondo (talk) 10:39, 16 May 2010 (UTC)[reply]

BSW-RMH (talk) 21:02, 13 May 2010 (UTC)[reply]

Prognosis

Minor suggestion: The second paragraph could be clearer if you state at the beginning that most of the complications that are life-threatening result from either muscle coordination issues or behavioral changes resulting from the decline in cognitive function (rather than just: symptoms). —Preceding unsigned comment added by BSW-RMH (talk • contribs) 21:23, 13 May 2010 (UTC)[reply]

Done, seems to help - although heart disease being second most common cause doesn't seem to be covered by this statement, so maybe we need a provisio at the start 'apart from heart disease ...' ? Lee∴V (talk • contribs) 14:09, 16 May 2010 (UTC)[reply]

I may be wrong-but I think the heart disease is usually heart failure as involuntary heart muscle coordination by the brain is eventually lost? So maybe just a reword to say "voluntary (ex., skeletal muscle which controls body movement) and involuntary (ex. heart muscle which controls heart function) muscle...", this is a bit awkwardly stated to try to make it not so technical. There's probably a better way :) BSW-RMH (talk) 15:25, 20 May 2010 (UTC)[reply]

~~Again very minor, but the word 'understandable' in the following sentence may be considered POV.~~

" It is unclear to what extent suicidal thoughts are influenced by psychiatric symptoms, as they may be considered to be an understandable response of an individual to retain a sense of control of their life or to avoid the later stages of the disease." BSW-RMH (talk) 21:14, 13 May 2010 (UTC)[reply]

Done. As above so minor that if I had been you I would have rather fixed it. Nevertheless I agree completely.--Garrondo (talk) 16:23, 14 May 2010 (UTC)[reply]

Epidemiology

I suggest expanding this section to give more information of the prevalence of the disease worldwide. Here is a useful summary quoted directly from a WebMD article which relies on the primary reference listed below.

"United States Several epidemiologic studies in the United States, conducted from 1945-1980, show consistent statistics stating that approximately 30,000 people have HD. Recent estimates of the prevalence of HD in the United States are between 5 and 10 people per 100,000. International HD occurs in various geographic and cultural ethnicities worldwide. The worldwide prevalence of this disorder is 5-10 cases per 100,000 persons. In North America and Europe, HD has a prevalence of 0.5-9.95 cases per 100,000 individuals. The prevalence of HD in the United Kingdom is currently estimated at 8 cases per 100,000 individuals. In a study by Walker et al in South Wales, a prevalence of 7.61 cases per 100,000 persons was reported. This study was reanalyzed in 1988 and showed the prevalence to be higher (8.85 cases per 100,000 persons), indicating a slight rise over the years. The prevalence in Japan is estimated at 1 case per 100,000 people."

http://emedicine.medscape.com/article/289706-overview
Driver-Dunckley E, Caviness JN. Huntington's Disease. In: Schapira AHV. Neurology and Clinical Neuroscience. Elsevier; (2007):67: 879-885.

BSW-RMH (talk) 21:35, 13 May 2010 (UTC)[reply]

I have added the worldwide prevalence using both references. All the other rates seem quite unspecific (0.5 to 9.95 in Europe) or too similar to the world prevalence (5-10 cases in US) so I have left them out.--Garrondo (talk) 08:25, 16 May 2010 (UTC)[reply]

I have been keeping an eye out for a decent review that gives more recent worldwide statistics, so far any decent references only cover global and one specific part of the world so have to be cobbled together to give a more complete picture, but is not ideal. Note the oxford monographs covers the most I've seen but is still not a complete picture. I've noticed in my editing how hard it is to find references for high level stats like this, which one would have thought would be available! Lee∴V (talk • contribs) 14:18, 16 May 2010 (UTC)[reply]

It's definitely not easy :) It may reflect the sponsorship of the research/publications usually being at the national level. I've noticed the WHO usually gives the best worldwide epidemiology data, but they are heavily focused on infectious diseases, and factors that affect overall mortality/nutrition. The degenerative diseases seem to be more of an issue in countries with longer mean life spans. BSW-RMH (talk) 15:31, 20 May 2010 (UTC)[reply]

Ok .. I'll add to todo for future ref... Lee∴V (talk • contribs) 11:27, 3 June 2010 (UTC)[reply]

Society and culture

The ethics section is well-written and interesting but applies to any genetic disorder. It seems more appropriate for this section to be included in the Wiki article on Genetic testing.

BSW-RMH (talk) 21:41, 13 May 2010 (UTC)[reply]

I only partially agree on this one, since while it is true that it applies for any genetic disorder it is agreed in secondary sources that many of the ethical issues began with HD which finally become a model for other genetic diseases. Additionally as you say most people consider quite interesting. Finally most of the sources specifically talk about HD. I believe we should leave it, although the genetic testing article may benefit from duplicating some info into it.--Garrondo (talk) 06:35, 14 May 2010 (UTC)[reply]

The genetic testing article wasn't in good shape when we got to this section, so we wrote our own ( i.e.. with references etc.). The idea being to improve the testing article and move the info across at some future date. Hence why you've noticed the slight 'general' tone of the section.. So yes should move, but until the testing article reaches a better standard should keep the section for now Lee∴V (talk • contribs) 14:50, 16 May 2010 (UTC)[reply]

I see what you mean and it is really improtant to note the importance of HD in raising these ethical issues. In that case, maybe you could add a sentence or two to the beginning of this section pointing out that the HD field pioneered many ethical debates that now extend to other genetic disorders, and maybe emphasize the specific events that led to ethical contributions from the HD field-like the advent of the first diagnostic test for HD. BSW-RMH (talk) 15:43, 20 May 2010 (UTC)[reply]

Thanks to the reviewer for his time, effort and also for the grasp she has reached in only a few days of how wikipedia works (and feels). I will try to address the comments she proposes as soon as possible. Bests.--Garrondo (talk) 06:38, 14 May 2010 (UTC)[reply]

Yes, top marks! This article has been blessed with a series of great reviewers and their//your input should have much greater recognition - not that many readers in general appreciate the scale of effort that goes into some of the articles they read. The amount of effort that goes into fact checking and thoughtful consideration - then to put into a constructive framework is amazing and requires skill, combine this with the amount of time spent behind the scenes ( on discussion page and in peoples thinking / searching /reading / verifying time) compared to the actual edits to good WP articles belies belief! Lee∴V (talk • contribs) 14:50, 16 May 2010 (UTC)[reply]

You're heartily welcome. It was enjoyable and challenging to work on such a well-written article! It is amazing how much work, time, and expertise you have all voluntarily contributed to make this article so comprehensive. Well-done! BSW-RMH (talk) 15:43, 20 May 2010 (UTC)[reply]

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Fatal?

consensus reached Dubbin^{u | t | c} 18:15, 13 June 2016 (UTC)[reply]

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As I was reading the lead due to review above a sentence jumped into my eyes: Although the disorder itself is not fatal,. Of course it is fatal. I mean, everybody finally dies from the consequences of the disease. The disease produces muscular problems which earlier or later kill you, and nobody can really stop it. Of course it is not a heart atack that intstantly kills you but it is similar to saying that a tumor does not kill you... A tumor deteriorates the normal functioning of different organs and that in turn earlier or later kills you. HD is probably slower but the result is the same. If HD wasnt fatal life expectancy would be the same, or almost the same, which clearly is not. This same sentence appears in differente wikipedia articles on neurodegenerative diseases and I believe it is simply a way of being politically correct and comforting those with the disease that come to read the article, but we have to remember that we do not writte for patients or doctors but for a general audience.

I have finally eliminated tbe sentence from the lead and prognosis sections and the thruth is that sounds almost the same ... (which is probably additional hint that it was only politically correct langauge).

Bests.--Garrondo (talk) 16:40, 14 May 2010 (UTC)[reply]

I agree. BSW-RMH (talk) 17:10, 14 May 2010 (UTC)[reply]

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On penetrance

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Reading the inheritance section I have discovered that the explanation we made of the disease was not completely accurate. We said that since the disease was inherited autosomally dominantly 50% of the offspring would have the disease, but this only occurs in those diseases almost fully penetrant. Having the disease is a phenotype and there are diseases that although transmitted genetically in an autosomal dominant way less than 50% of individuals show the phenotype. I have tried to fix it along all the section (although I am not very sure on wether I was succesfull). Bests.--Garrondo (talk) 17:00, 14 May 2010 (UTC)[reply]

Hmmm, we only have one mention of phenotype in the article, ( maybe subconsciously to avoid another technical term to introduce to casual readers? ). Maybe this is an area we should expand and explain in context? Lee∴V (talk • contribs) 14:54, 16 May 2010 (UTC)[reply]

I am not very sure if it is needed or if it is enough with what there is now. Nevertheless genetics is not my strong point... Maybe the reviewer or any other external reader could give us a hint on the issue... Thoughts anybody?--Garrondo (talk) 17:30, 16 May 2010 (UTC)[reply]

The genetics part looks accurate to me as it is right now. The Inheritance section below needs a little tweaking:

"Since penetrance of the mutation is very high those who have a mutated copy of the gene will have the disease. In this type of inheritance pattern, each offspring of an affected individual has a 50% risk of inheriting the mutant allele and therefore being affected with the disorder (see figure)."

A person with 'the mutation' will not necessarily have the disease, depending on what you mean by 'the mutation', because there are so many variations of the repeat expansion. Penetrance is variable with the number of trinucleotide repeats as noted in the previous section of the article, with more than 40 being fully penetrant (indivuduals will get the disease in their lifetime), 36-40 having reduced penetrance (may or may not get it), 28-35 are phenotypically normal (no disease) but these mutations are genetically unstable and can sometimes expand in male gametes so that their children end up with more than 35 repeats and therefore are at risk of having the disease even if their parents did not.

"This probability is sex-independent.[17]"

While the inhertiance of the gene is not sex-linked (meaning the gene is on the X or Y chromosome), the probablity of inheritance is affected by the sex of 28-40 repeat carriers due to the differences in stability of the intermediate expansions during spermatogenesis (highly unstable) relative to oogenesis (relatively stable). Thus children have a higher probablity of inherting a disease-causing mutation (with an expanded repeat higher than what their father had) if their father is a 28-40 copy carrier than if their mother is. (reviewed in Myers 2004, cited below)

"Trinucleotide CAG repeats over 28 are unstable during replication and this instability increases with the number of repeats present.[15] This usually leads to new expansions as generations pass (dynamic mutations) instead of reproducing an exact copy of the trinucleotide repeat.[13]""

This is accurate, but could benefit from mention that the most significatn instability/expansions occur during paternal inheritance. Oogenesis introduces expansions or contractions of less than 5 repeats, whereas spermatogenesis is prone to incorporate larger numbers of repeats (up to 41). (Myers 2004, Duyao 1993)

Meyers RH. Huntington’s Disease Genetics. NeuroRx. (2004); 1(2): 255–262. PMC534940

Duyao M, Ambrose C, Myers R, Novelletto A, Persichetti F, Frontali M. Trinucleotide repeat length instability and age of onset in Huntington's disease. Nat Genet. (1993);4(4):387-92. PMID: 8401587

BSW-RMH (talk) 17:00, 20 May 2010 (UTC)[reply]

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Creation of the HDF

article created Dubbin^{u | t | c} 18:15, 13 June 2016 (UTC)[reply]

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I wanted to do some useful but mind-easy work and I have created the Hereditary Disease Foundation article copying some parts from this one. A stub for the moment but one red link less... :-) (I have also noticed that it was created in the past and eliminated due to copyright problems). Included a copyright notice here.--Garrondo (talk) 18:12, 16 May 2010 (UTC)[reply]

Nice one, I had an eye on it but was thrown off by the 'please inform deleting admin first' note - guess I should have been as bold as thyself! Am still plowing threw the history books and there's plenty of info for expansion when I get further in! Thanks Garrondo ! Lee∴V (talk • contribs) 12:31, 17 May 2010 (UTC)[reply]

I did not see the notice... I suppose nobody really cares much. Anyway I am sure that it has no copyright problems and I am watching it (and I suppose same happens with you) so I doubt there are any problems for not informing deleting admin first...--Garrondo (talk) 12:46, 17 May 2010 (UTC)[reply]

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HD category

category created Dubbin^{u | t | c} 18:15, 13 June 2016 (UTC)[reply]

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When creating the above article I added to the Huntington's disease category and discovered that it did not exist. I have created it and added to some of the most important pages. It would be useful to have it on mind to add it to other articles. Bests.--Garrondo (talk) 18:25, 16 May 2010 (UTC)[reply]

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On ethics

no change without citation Dubbin^{u | t | c} 18:15, 13 June 2016 (UTC)[reply]

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The article contained two sentences claiming that there was a global or national consensus that all testing on minors was unethical. The sources contained the opinions of a handful of specific doctors--this is insufficient to claim a consensus for what is surely a high contentious issue.

According to how the article was previously written, a teenager should not be tested, regardless of their desire. Whatever alleged harm there is in testing them, I am pretty sure that there is a widely held counterargument that teens have the right to know not only so that they may plan for the future (long term care isn't cheap), but also so that they'll know right away whether they have a 50% chance of passing the gene (and thus the disease) to their children.

I am not in possession of any statistical numbers (neither were the sources), but I am fairly certain that there is no consensus for denying Huntington testing to sexually active teens, nor for families of limited means that require a long term financial plan. I find it very hard to believe that the majority of certified doctors endorse a such a pro-ignorance view, so I have changed the offending lines to refer to "some" doctors until solid evidence of this unlikely consensus is demonstrated.

--99.205.10.246 (talk) 02:32, 13 June 2010 (UTC)[reply]

I did not find any sources saying that testint on minors is Ok; which does not mean by any means that they are not there. Until you bring them we will leave the text as it was. We can not work on personal opinions but on reliable sources. Bests.--Garrondo (talk) 08:01, 13 June 2010 (UTC)[reply]

Strange how the people who insist on rule quoting the most (e.g. reliable sources, personal opinions, blah blah blah) also tend to be the least capable of reading comprehension. The sources do not support the statements in the article. Period. Saying Dr. A, Dr. B, and Dr. C have argued such and such does not demonstrate a consensus. Claiming you haven't found any other opinions (I rather doubt you looked very hard) does not demonstrate a consensus, i.e. failing to find sources saying that testing minors is OK is not the same thing as demonstrating a consensus that testing them is not OK. It is ridiculous to assert, in absence of VERY COMPELLING sources, that all doctors believe that even sexually active teens should be denied access to Huntington testing. The also strongly implies that all minors are "cognitively immature", which (assuming age of majority = 18) few doctors would unconditionally agree with. The fact that someone has taken the time to dig up 3 opinions that happen to support their own is irrelevant. I can find 3 opinions that the sky is red if I tried hard enough. To demonstrate consensus, you must actually find a survey of some sort (surveys are the best you can do, because this isn't a question of hard science.) Until then, I am removing the offending lines. One does not require source to remove patently ridiculous material; one merely requires the lack of a source. And there isn't one. You, on the other hand, require a source for re-insertion. And if you do find a source that supports such a consensus, please specify in the article precisely where this consensus exists (e.g. doctors worldwide? UK doctors? Members of organization X only?) -98.230.53.210 (talk) 23:00, 2 October 2010 (UTC)[reply]

Again: references we have have been judged to be valid and they do say that there is consensus on not testing minors: so again, feel free to bring a source that says the opposite before any changes. Also stop doing personal attacks such as "the least capable of reading comprehension". I feel I am quite capable of reading. Finally it would be great if you registered so communication could be easier.--Garrondo (talk) 07:38, 3 October 2010 (UTC)[reply]

Again: the sources make no such claim. As I recall one of the UK sources offhandly mention there being a consensus, though it isn't even clear amongst whom the consensus is supposed to exist, much less the evidence to support this alleged consensus. The section is written so disgustingly manipulatively that it isn't even totally clear that this alleged consensus, which those sources do NOT adequately support (an extremely brief offhand mention is not enough), is ostensibly one amongst doctors. The consensus of doctors is enough to support medical statements of fact. The consensus of doctors is not nearly enough make ethical pronouncements for the entirety of humanity. This is why it is vital that this alleged consensus is explicitly spelled out, not vaguely alluded to. This isn't Special Relativity; it's ethics. A doctor isn't any more qualified than you or I to say what is or isn't the right thing to do. If a consensus amongst doctors exists, it definitely deserves to be mentioned, but it needs to be properly and explicitly identified as such. If the term "ethics" here is meant to apply only to doctors' professional code ethics (as opposed to a parent's decision to test being "ethical" or "unethical"), that too needs to be explicitly spelled out. And sorry, but it is not a personal attack to say that someone did not comprehend what they read if they characterized my edits here as an attempt to insert personal opinions. --98.230.53.210 (talk) 21:32, 17 November 2010 (UTC)[reply]

I second Garrondo here -- there would need to be at least one reputable source arguing that testing minors is okay in some circumstances. Looie496 (talk) 16:39, 3 October 2010 (UTC)[reply]

I never edited the article to include any statement arguing that testing minors is ok. I merely changed the language to remove references to this non-proven consensus. I could add three separate sources from reputable scientists to the article on, say, string theory that says it is flawed. This is not enough to demonstrate a consensus... and your argument is even more absurd in this case. "Consensus" here does not refer to agreement on some objective fact, like the speed of light. Ethics are never objective. Rather, the only objective fact to be supported or rebutted by sources would be the existence of such a consensus. In other words, objective statements need only verification from a few independent sources for us to say there is a consensus. However, subjective statements (like ethical pronouncements) are never true or false and should never be included in Wikipedia without qualification. On the other hand, the meta-statement "there is a consensus on subjective statement X" IS objective. This meta-statement is the one that must be supported by a source. You could have a hundred sources supporting the original statement and it still wouldn't be valid for unquoted inclusion in Wikipedia, because, without a supporting source, the implicit or explicit assertion of the meta-statement (the existence of a consensus) is always Original Research. Saying that Huntington's testing on minors is unethical is subjective. Saying that there is a consensus (AMONGST A CERTAIN GROUP OF PEOPLE) regarding Huntington's testing on minors is objective. And no one has brought a valid source for that objective statement. Again, the only source that mentions a consensus did so in an unscientific manner and did not even specify amongst whom this consensus exists.

The section on ethics is an unsupported, weasel-word infested ("some issues"), manipulative pile of drivel. It doesn't enlighten; it distorts and preaches. However, I won't bother editing again. I simply do not have the tenacity to win against those who, through ignorance or malice, repeatedly misrepresent sources and Wikipedia's guidelines. --98.230.53.210 (talk) 21:32, 17 November 2010 (UTC)[reply]

I will ignore all your personal attacks, assumptions of bad faith, and shouting. I will only say as farewell that we will be waiting for you to come back with a ref that says that there is no consensus and I will happily add it. Editors in this article only aim to have as good quality as possible.Bests.--Garrondo (talk) 08:12, 19 November 2010 (UTC)[reply]

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expansion of aggregate function

consensus reached Dubbin^{u | t | c} 18:15, 13 June 2016 (UTC)[reply]

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A recent edit added by User talk:Ashley Vuong the following to the 'Cellular changes due to mHtt' section: 'The polar nature of glutamate causes interactions with other proteins when glutamate is overabundant in Htt proteins. Thus, the Htt molecule strands will form hydrogen bonds with one another, forming a protein aggregate rather then folding into functional proteins. Over time, the aggregates accumulate, ultimately interfering with neuron function because'...

'Neuronal inclusions run indirect interference. The excess protein aggregates clump together at axons and dendrites in neurons which mechanically stops the transmission of neurotransmitters because vesicles (filled with neurotransmitters) can no longer move through the cytoskeleton. Ultimately, over time, less and less neurotransmitters are available for release in signaling other neurons as the neuronal inclusions grow.'

Although plausible this needs a reference, and may be better off placed in the huntingtin article in anycase. Lee∴V (talk • contribs) 10:58, 18 September 2010 (UTC)[reply]

I agree since it is probably too much specific for the main article.--Garrondo (talk) 06:27, 21 September 2010 (UTC)[reply]

Unless this is sourced to WP:MEDRS-compatible secondary sources, it should be trimmed down. JFW | T@lk 09:15, 21 September 2010 (UTC)[reply]

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References layout

layout altered Dubbin^{u | t | c} 18:20, 13 June 2016 (UTC)[reply]

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On my screen I have an ugly white space between the "References" header and the actual start of the references, with only a relatively small image to the right. Also, the references are difficult to read, because they are forced in 2 columns and I have a pretty wide screen, so that makes for very long lines in small type... Perhaps the {{clear}} template could be removed and the "2" replaced by "35em" (making column number variable depending on screen width). Given the near perfect state of this article, I did not make these edits, assuming that there is perhaps a good reason for this that I don't know about... :-) --Crusio (talk) 18:08, 24 January 2011 (UTC)[reply]

I've changed the refs to use variable numbers of columns, using 30em which I think is the standard. I've changed the picture layout to remove the white space, but it may be necessary to take further steps to improve the layout. Both the pictures near the bottom of the article are essentially there just to add interest to the article, rather than being significantly informative, so perhaps one could be removed.-gadfium 19:30, 24 January 2011 (UTC)[reply]

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Claim of "first autosomal disease locus found using genetic linkage analysis"

consensus reached Dubbin^{u | t | c} 18:20, 13 June 2016 (UTC)[reply]

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Although the cited article may indicate this, is it in fact true? For instance, the CFTR gene of Cystic fibrosis was found on Chromosome 7, an autosome, by genetic linkage analysis in 1989. The citation is Rommens JM, Iannuzzi MC, Kerem B, Drumm ML, Melmer G, Dean M, Rozmahel R, Cole JL, Kennedy D, Hidaka N (1989). "Identification of the cystic fibrosis gene: chromosome walking and jumping". Science. 245 (4922): 1059–65. Bibcode:1989Sci...245.1059R. doi:10.1126/science.2772657. PMID 2772657. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link) Thanks — $Q$ uantling (talk | contribs) 17:18, 25 October 2011 (UTC)[reply]

This is why we need secondary sources for such claims. JFW | T@lk 22:12, 25 October 2011 (UTC)[reply]

I would regard the above statement as very dubious. HTT & CTFR were unusual because, although the genetics was well understood, locating the relevant genes proved difficult using techniques available before the mid- late-1980s. A quick scan of an old Genetics textbook^[1], provides a human autosomal linkage map showing at least 8 genes mapped on Chromosome 1 (a snippet is visible on Google Books). The diagram is redrawn from McKusick (1972)^[2]. I think this demonstrates that a number of human autosomal genes had been mapped using linkage analysis prior to 1972, and long before the work on HTT. Relevant references below. Semudobia (talk) 10:22, 23 January 2016 (UTC)[reply]

^ Ursula Goodenough; Robert Paul Levine (1 January 1974). Genetics. Holt, Rinehart and Winston. p. 531. ISBN 978-0-03-084490-4.
^ Victor A McKusick (December 1972). "Human Chromosome Mapping Newsletter" (PDF). {{cite journal}}: Cite journal requires |journal= (help)

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Inadequacy of dmoz for external links

consensus reached Dubbin^{u | t | c} 18:20, 13 June 2016 (UTC)[reply]

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The dmoz directory of Huntington's disease links omits many sites I would consider among the most widely used, important and reliable for professionals and family members alike. Among those missing are:

Doubtless there are others. I have submitted requests repeatedly for sites to be added to the directory over several months, and these have been ignored.

Unfortunately I am forced to conclude that the directory is either untended or is in the hands of people (or a person) who wishes to exclude relevant links for reasons of their own.

I'm afraid I don't have the time to become a dmoz editor, and I fear that other people's requests are being ignored too.

I suggest that the 'External Links' section needs to be hosted locally here in order to restore its currency and accountability.

Pending discussion, I suggest we favour the inclusion in the article of references and internal Wikilinks to relevant organisations that have WP pages. Dubbin (talk) 19:39, 4 December 2011 (UTC)[reply]

Ed, it is pretty hard to decide whether any external link is suitable without a bit more information about a site. WP:ELNO is a guideline that discusses the suitability (or lack thereof) of particular kinds of external links. I would wish to restrict the list to national organisations in English-speaking countries, and the very large (national or even international) research charities. Anything less will just make it very granular, and less relevant for readers who do not actually need to learn about the HD association of a small town in the middle of nowhere.

Can I suggest you provide a description for all the above links, so we can judge them on their merits without having to personally crawl each and every one of them? JFW | T@lk 23:12, 4 December 2011 (UTC)[reply]

I'll put together a more comprehensive list of top tier sites, with descriptions, geographically categorised, and report back here when it's ready for scrutiny Dubbin (talk) 18:14, 5 December 2011 (UTC)[reply]

OK, please see this draft page for a proposed top-level external link list. Note that the headings are placeholders to explain my inclusion criteria and will need simplifying, or omitting, for the article. I've left some comments in italics for a couple where I wasn't sure. Comments and suggestions welcome, here or in the associated talk page. There's no hurry here - we want this to be short and authoritative, so let's get a good list agreed before proceeding, then be stringent with new additions. Thanks Dubbin (talk) 13:51, 8 December 2011 (UTC)[reply]

I think all those links are reasonable, but I would drop the one that is run like a forum and possibly those that you rightly marked "too granular". Perhaps a few other contributors might wish to comment with the view to get some form of consensus. JFW | T@lk 19:30, 18 December 2011 (UTC)[reply]

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Name

no objectionsDubbin^{u | t | c} 18:20, 13 June 2016 (UTC)[reply]

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I've amended the article to reflect that the term 'Huntington's chorea' is defunct and 'Huntington's disorder' was never widely used. I've added a detailed note in the History section and citations explaining the rationale for the change; there are plenty more (e.g. http://www.guardian.co.uk/styleguide/h) but I don't want to swamp the article. Dubbin^u | t 17:40, 18 December 2011 (UTC)[reply]

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Proposed external links

addition agreed Dubbin^{u | t | c} 18:20, 13 June 2016 (UTC)[reply]

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I'm transferring these here for comment and suggestions. I propose to transfer the final list to the article on 30th December. See discussion above for rationale (in short, the Open Directory listing isn't meeting the needs of the article). Per WP:ELNO the list should be restricted to national organisations in English-speaking countries, and the very large (national or even international) research charities.

I support the current list as added to the article. Sorry for the fact that no other contributors were prepared to respond to your suggestions. JFW | T@lk 21:19, 31 December 2011 (UTC)[reply]

Amazing list of links, well done! NCurse _work 08:05, 3 January 2012 (UTC)[reply]

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Research directions

no reply Dubbin^{u | t | c} 18:20, 13 June 2016 (UTC)[reply]

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It has been noted that the "Research directions" section of this article is more current than the article it nominally summarizes. The attention of editors here to updating Huntington's disease clinical research would be helpful. LeadSongDog come howl! 14:23, 22 January 2012 (UTC)[reply]

Editors' thoughts on whether the separate article should be kept or deleted, would also be appreciated. Please contribute to the discussion on its talk page. Dubbin^{u | t | c} 14:33, 22 January 2012 (UTC)[reply]

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Caspase-6 cleavage of mHtt

not added Dubbin^{u | t | c} 18:20, 13 June 2016 (UTC)[reply]

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I'm surprised this bit is missing - the 2006 Graham paper from Cell showing that caspase-6 mHtt cleavage is required for R6/2 mouse HD neuronal degeneration - so I added it. Sorry if it's been through the wringer already, but I didn't see anything much in the archives. There's also the earlier paper, Wellington CL, et al. (2002) Caspase cleavage of mutant huntingtin precedes neurodegeneration in Huntington’s disease. J Neurosci. 22:18, 7862-72. Jon (talk) 11:28, 2 March 2012 (UTC)[reply]

Much too premature to discuss this line of research. You have not provided data that inhibiting caspase 6 improves end points in mice, let alone humans. We can only discuss treatments that have been discussed in secondary sources and are expected to be widely useful. JFW | T@lk 12:59, 2 March 2012 (UTC)[reply]

Agree completely. Furthermore, caspases have emerged as essentially impossible to drug with small molecules and are no longer widely considered viable therapeutic targets Dubbin^{u | t | c} 18:16, 2 March 2012 (UTC)[reply]

Please see new section following, with compliments on the overall, continuing quality of this article. In re: this general discussion, please consider. It may be worth having lines inserted in various relevant places that can change with time, reporting active areas of research inquiry. That is, in this informed opinion, it is better to have such information present in brief statements and to change it as understandings change, than to miss the opportunity to allow a reader to make a general connection that promotes potentially insightful and productive thought (e.g., here, caspases/proteases and their function in disease states), whether or not the vein ultimately proves most important for Huntington's. Finally, a philosophical point from a DD professional, with much respect for contributor Dubbin et al: Before Gleevek, kinases were not druggable targets, and in fact much argument was given to support this erroneous conclusion. Many classes of targets are not considered so, and argument accrues to justify such conclusions ... until the first in class is discovered. Then, lo and behold, the tenor of the literature changes. Hence, as one who writes and reviews such papers on targets and their viability (and, though with no current interest, as one who has specifically prepared and tested Cys protease inhibitors), I would encourage caution vis-a-vis intrenching any strong opinion about what can and cannot ultimately be targeted. Negative results (and arguments) are always the weaker. Cheers. LeProf. — Preceding unsigned comment added by 67.175.245.235 (talk) 05:14, 14 November 2012 (UTC)[reply]

Thank you for this thoughtful comment. I agree that we need to keep an open mind about experimental approaches. I'd say the main reason for not including caspase-6 cleavage yet is that sufficient evidence has not been advanced for it to meet the Wikipedia guidelines for inclusion (secondary sources as cited above by JFW). Poor druggability at the present time is, I suggest, one reason why such evidence does not yet exist - not a reason for non-inclusion per se. Wikipedia is an encyclopedia, not a crystal ball, so we have to wait until the problem is solved before we discuss it in this article. But Wikipedia is the ultimate in open-mindedness: however the article is phrased now, it can always be updated in the light of new evidence. Dubbin^{u | t | c} 11:21, 14 November 2012 (UTC)[reply]

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New link (HDYO)

no objections Dubbin^{u | t | c} 18:20, 13 June 2016 (UTC)[reply]

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An anonymous editor has added http://hdyo.org to the list of support organisations. HDYO is the Huntington's disease youth organisation and is well-supported and well-credentialled, and I would support its inclusion, but I thought it might be worth discussing here since HDYO is also quite new - launched February 2012. Dubbin^{u | t | c} 11:53, 28 June 2012 (UTC)[reply]

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Diagnosis

no consensus to alter Dubbin^{u | t | c} 18:20, 13 June 2016 (UTC)[reply]

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The page stated that imaging was not helpful in the diagnosis, and that cerebral changes were only visible late in the disease. I changed the page a while ago to say that HD was diagnosable by MRI and it was changed back. I had a patient who was diagnoses by MRI as their relatives would not allow blood testing. Even the illustration in the article says notes the changes HD. The diagnosis is made by characteristic changes in the caudate nuclei. — Preceding unsigned comment added by Andrew Nielsen (talk • contribs) 07:46, 30 June 2012 (UTC)[reply]

The presence of changes seen in HD does not mean the MRI could or should be used to diagnose the disease. The changes are non-specific as any HD specialist will tell you, and are seen in HD-like conditions (such as HDL2). This is not the place to publish case reports. Genetic testing is the only way the disease can be diagnosed with certainty. To say otherwise in an article for the public is irresponsible and misleading. Dubbin^{u | t | c} 18:41, 1 July 2012 (UTC)[reply]

If someone presents with, say psychiatric symptoms and movement signs, and a family history of HD they will have an MRI before genetic results are available. The importance issue is that urgent medical conditions are excluded. The chance of someone having a HD-like disorder with a family history of properly diagnosed HD is vanishingly small. If you are concerned that stating the obvious about the MRI changes of HD is irresponsible, then I suggest you improve the differential diagnosis section to state which conditions in the differential have MRI findings that resemble HD. That would be the helpful, and therefore responsible, thing for you to do. Andrew Nielsen (talk) 09:55, 14 July 2012 (UTC)[reply]

I don't particularly want to dig through the history here, so let me ask: is there a high-quality review article in a medical journal that states that MRI is useful for diagnosing HD? Looie496 (talk) 18:05, 14 July 2012 (UTC)[reply]

I disagree with your assertion that every patient with a family history of HD will have an MRI. If you can find a reputable source that states that MRI is essential for diagnosing HD, please cite it. This may be your practice, but it is not standard practice everywhere. In my experience, neuroimaging of typical cases (which, of course, present slowly over several years) is not necessary because "urgent medical conditions" do not mimic HD. They are, in fact, "vanishingly" unlikely in the presence of a typical family history and clinical picture. The diagnosis section as it stands mentions that HD causes certain MRI changes but that these are not diagnostic. This is correct and authoritative. You are free to behave differently as a clinician but please don't expect Wikipedia to change to reflect the idiosyncrasies of your personal practice. As to HD-like conditions, detailed descriptions of these belong in the individual articles linked from the differential diagnosis section, not in the HD article. Dubbin^{u | t | c} 09:30, 15 July 2012 (UTC)[reply]

Huntington's disease can present with psychiatric symptoms such as psychosis. When someone presents like that no one will wait until the HD genetics are back before they do an MRI. Unfortunately, patients present "idiosyncratically". If I said, "Oh no, this can not be HD, as the presentation is acute," then I would be a laughing stock. A patient with DH who has not had MRI/CT brain would be a new thing to see. And, of course, I did not suggest that MRI was essential to diagnosing HD. I accept your point that the MRI will not distinguish between Huntington's-disease-like conditions. But, once a HD-like condition has been diagnosed, the vast majority of differentials fall away and it is clear that you are dealing with a neurological condition that does not have to be dealt with urgently. To ignore this important and obvious fact implies that nothing can be be done diagnostically until the genetic tests come back. There is not need to find a review article that says that MRI is useful in diagnosing HD: the fact that there are characteristic findings makes it obvious. Stating the same thing differently, if you wonder if someone has HD, and the MRI scan is positive, then the post-test probability is a LOT higher than the pre-test probability, isn't it? — Preceding unsigned comment added by Andrew Nielsen (talk • contribs) 05:29, 16 December 2012 (UTC)[reply]

You haven't said anything new and a Wikipedia talk page isn't the place to define clinical policy - the scientific literature is. Suffice to say there is enough disagreement and dissent from your 'MRI as diagnostic tool' position that yes, a WP:MEDRS-quality citation will be needed to get it into the article. For my part, I find your clinical position troubling. As an experienced HD clinician, I would say that you are flying dangerously in the face of established practice when you assert the value of an MRI in diagnosing psychiatric manifestations of HD, and in using the phrase 'the MRI scan is positive'. There aren't "characteristic" MRI findings - that's the point. If you disagree, find a suitable citation to support your position. Dubbin^{u | t | c} 19:54, 16 December 2012 (UTC)[reply]

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Bravo, thank you for quality, continuing improvements.

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Just reread parts, and skimmed the whole of this excellent article. Thank you to those who have contributed to its quality, and who continue to improve it. Cheers. LeProf — Preceding unsigned comment added by 67.175.245.235 (talk) 04:55, 14 November 2012 (UTC)[reply]

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GM1 and HD

no consensus to add Dubbin^{u | t | c} 18:24, 13 June 2016 (UTC)[reply]

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On Bloomberg web page and Bloomberg TV two years ago, there was a mention of animal (mouse) trials of a neuronal growth factor, GM1. If administered early to mice with HD it reduced chorea. If administered late it increased chorea. The mouse studies were so promising the review panel recommended immediate human trials. However there has been no word since then. Does anyone know what the story is? — Preceding unsigned comment added by 107.196.121.15 (talk) 05:07, 23 February 2013 (UTC)[reply]

This talk page is for discussion of the accompanying Wikipedia article, not a general discussion forum for its topic. The 'external links' in the article will take you to reliable sources of information and discussion about the latest research. Dubbin^{u | t | c} 12:23, 23 February 2013 (UTC)[reply]

I agree, but I don't think it will do any harm to give a pointer to http://www.news-medical.net/news/20121130/GM1-ganglioside-effectively-treats-patients-with-Parkinsons-disease.aspx. Looie496 (talk) 16:21, 23 February 2013 (UTC)[reply]

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Recent additions with some problems in sourcing

no objections Dubbin^{u | t | c} 18:24, 13 June 2016 (UTC)[reply]

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I paste here my comment to User talk:Webetnine regarding his additions to the article.

Hello Webetnine:

Thank you very much for your contributions to the Huntington's disease article. They look very interesting and clearly add value to the article. Howevever, the HD article is a featured article, and in this sense it is considered one of the best articles of wikipedia. In this sense sourcing has to be of outstanding quality. The sources you have added seem all more or less reliable, but some info on them is lacking, which would render unusable some of your content. It would be great if you could provide some more info on the sources. I would format it into the article:

Regarding the source: Carlson, Neil R. Physiology of Behavior. Boston: Pearson, 2013. Print I suppose it is a book, if so the pages that were used to source your addition should be added, or if it is an specific chapter with a different author we could cite the full chapter.

Regarding the source: HTT." - Huntingtin. N.p., n.d. Web. 06 May 2013 I am not really sure about what exactly do you mean with N.p and n.d, nor where did you find it. Moreover, since you say web I assume it is a web site in which case the url should be added.

Regarding the last source, (Kwan, 2012): it is a primary source (that is; an experiment). Wikipedia and more specifically should be based in secondary articles, i.e specialized books or review articles. See WP:MEDRS.

--Garrondo (talk) 08:30, 7 May 2013 (UTC)[reply]

The Carlson book is an undergraduate-level textbook of behavioral neuroscience, and therefore not a good source for this article. Looie496 (talk) 15:20, 7 May 2013 (UTC)[reply]

Specific revision we are talking about is here. If it is not fixed I will probably remove content in a few days and move it here for further discussion or improvement.--Garrondo (talk) 20:05, 7 May 2013 (UTC)[reply]

Similarly I have eliminated the following text:

In 1994 an international predictive testing protocol was initiated to aid genetic counselors in testing for HD. This included the recommendation that another person attend the sessions to provide support. This is also pertinent because the support person is dramatically affected by the test results. It has been documented that partner's experience shock and grief when a positive diagnosis for Huntington's is concluded. Only a small number of marriages dissipate due to the diagnosis. It was found that a partner's previous awareness and experience with the disease had a significant impact on how the diagnosis was perceived. ^[1]

Reasons for elimination is that all content is based in a primary source, and in addition is probably too specific and writting is not at the level of the article IMO. Some of the content could probably improve the article if polished and sourced better.

--Garrondo (talk) 20:16, 7 May 2013 (UTC)[reply]

^ Keenan, Karen (6th). "How Do Partners Find Out About the Risk of Huntington's Disease in Couple Relationships?". National Society of Genetic Counselors, Inc 2013. {{cite journal}}: Check date values in: |date= and |year= / |date= mismatch (help); Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)

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Research directions: glycemic control

no objections Dubbin^{u | t | c} 18:24, 13 June 2016 (UTC)[reply]

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I've removed recently added content on glycemic control as a research direction. This approach is decidedly niche, as attested by the sole primary source from 2009 that accompanied the text. It has not featured in any major review of therapeutic directions. There have been no human trials either. In any event the text was far too detailed (several times longer than 'improving neuronal survival'). If an editor is desperate to see it mentioned (and is free from conflict of interest), a more appropriate approach would be adding a much shorter section to the companion article Huntington's_disease clinical research. But MEDRS sources would be needed even for that. Dubbin^{u | t | c} 05:50, 25 May 2013 (UTC)[reply]

The discussion above is closed. Please do not modify it. Subsequent comments should be made on the appropriate discussion page. No further edits should be made to this discussion.

Requested move 23 April 2015

The following is a closed discussion of a requested move. Please do not modify it. Subsequent comments should be made in a new section on the talk page. Editors desiring to contest the closing decision should consider a move review. No further edits should be made to this section.

The result of the move request was: not moved. Favonian (talk) 21:37, 30 April 2015 (UTC)[reply]

Huntington's disease → Huntington disease – According to Wikipedia:Manual of Style/Medicine-related articles#Article titles we should use the scientific or recognised medical name that is most commonly used in recent, high-quality medical sources. The possessive use of the eponym in disease names is also discouraged as it can confuse people by implying that Huntington had the disease. Here are sources that use either form:

Sources that use "Huntington disease"

Sources that use "Huntington's disease"

gobonobo ⁺ ^c 22:22, 23 April 2015 (UTC)[reply]

Comment Gobonobo In a perhaps more general view results in Ngrams indicate an approximate 5:1 prevalence of use in favour of Huntington's disease. Is there a case for something like official name? Greg Kaye 10:18, 24 April 2015 (UTC)[reply]

Thank you for the Ngrams link. I had looked at references to both terms in Google Scholar and found that Huntington's disease had 98,500 results while Huntington disease had 159,000 results. Basic google searches for the terms showed a slight preference for the non-possessive (2.58 million for Huntington and 2.44 million for Huntington's). The links I provided above are probably the closest we're going to get to an "official" name and show that both are used by high-quality medical resources, again with a preference for Huntington. gobonobo ⁺ ^c 19:09, 24 April 2015 (UTC)[reply]

While, for me, precision takes priority over minutia details of recognizability, unless there is something to say that "Huntington's disease" is somehow incorrect, I think that the common recognisability of that name, which I don't personally think should be overly challenged by University textbook usage etc., should likely carry.

Propose amendement to the lead to read: "Huntington's disease or Huntington disease (HD) is a neurodegenerative genetic disorder that affects muscle coordination and leads to mental decline and behavioral symptoms."

Greg Kaye 09:22, 25 April 2015 (UTC)[reply]

Support Agree we should generally go with the World Health Organization. Doc James (talk · contribs · email) 13:01, 24 April 2015 (UTC)[reply]
Oppose, not that major of a name change, but looking at the page references and external sources the overwhelmingly common name seems to be Huntington's disease. Randy Kryn 18:50, 24 April 2015 (UTC)[reply]
Oppose: echoing Randy Kryn above.:
Support: Per the following discussion and the answer received back. (My further comment in indent below): Here is another link to a charity-driven group: HD Reach. Please contact any of these brilliant professionals on this clinical sites page: HD Reach: Medical Care: Clinical sites and inquire as to how they would feel with this proposal. I just wish Simple English Wikipedia would move their article from Huntington's chorea. It was unilaterally moved due to being 'more usual' as a name. That seemed to push back the clock back to the 'dark ages'. Fylbecatulous talk 21:57, 24 April 2015 (UTC)[reply]

Moved the simple wikipedia page back and contacted one of the HD researchers. I'll let you know if they reply. gobonobo ⁺ ^c 22:26, 24 April 2015 (UTC)[reply]

Gobonobo, thank you for the page move at Simple. That in itself has made this discussion invaluable. Progress there can be rather intractable... Fylbecatulous talk 22:48, 24 April 2015 (UTC)[reply]

@Fylbecatulous: The HD researcher got back to me and here is her reply: "The trend is clearly moving to Huntington disease without an apostrophe--the preponderance of use, possibly even now, would include the apostrophe, but the trend is away from it--and most editors are moving in that direction as well." gobonobo ⁺ ^c 21:43, 29 April 2015 (UTC)[reply]

@Gobonobo:, (I love the yo...) Thank you. Well that is amazing. On the basis of this report I am going to change my !vote to 'support' above. These professionals are cutting edge and if they say change is happening, I will echo that. Fylbecatulous talk 21:51, 29 April 2015 (UTC)[reply]

In this case I'd like to 'weigh in' as an HD researcher with 10 years' experience, a PhD in biomarkers for Huntington's disease and >30 publications in the field. Both terms are acceptable; I disagree that there is a strong trend for change; and there is no compelling reason to rename the article. By the way I'm this guy: https://iris.ucl.ac.uk/iris/browse/profile?upi=EJWIL36. I also founded and run http://hdbuzz.net which is the most popular source of HD research news for the global community of HD families. Our house style is to call it Huntington's disease because that's what real people actually call it. Dubbin^{u | t | c} 12:45, 30 April 2015 (UTC)[reply]

sigh. such hostility everywhere on Wikipedia. A little unnecessary to further remark in this sub-indent since you have already opposed below with quite good rationale. I am in America, as are these researchers and you appear to be in the UK; reiterating what you stated regarding the cultural / locational difference. Attempting to trump the credentials of my researchers with yours seems a bit unnecessary, since I only asked a simple request, that amazingly was answered. Peace and all the best. Fylbecatulous talk 16:39, 30 April 2015 (UTC)[reply]

Oppose This kerfuffle has been going on for years for a whole bunch of diseases; it's very annoying. The reasons for changing are not compelling, so we should stick to the older and more familiar name. Looie496 (talk) 15:50, 25 April 2015 (UTC)[reply]
Oppose. It would appear that a majority of references cited in the article use "Huntington's." Plus, it is the common name. Calidum T|C 19:12, 25 April 2015 (UTC)[reply]
Oppose. Both terms are used, and the split is to some extent an English v American one, as noted on the first item on this discussion page. Wikipedia explicitly avoids endorsing American or British spellings. However it is not clear-cut, since (for example) we have the UK Huntington's Disease Association; the Huntington Society of Canada; and the Huntington's Disease Society of America. Moreover taking issue with 'possession' is a straw man, because the apostrophe-s is used to indicate association as well as possession - as in "a week's time". Finally, citing journal metrics on this is misleading, as authors are required to obey journal house styles even if they disagree with them (I am a coauthor on a recent review entitled "Huntington Disease" even though I and a number of coauthors would never have used that form). Dubbin^{u | t | c} 11:57, 27 April 2015 (UTC)[reply]
Oppose - To the average person the solitary "Huntington" would sound unnatural but "Huntington's" on the other does sound natural. The latter is also the common name. There is also a general move away from eponymous syndromes to more pathognomonic nomenclature so we should change the article title when and if that happens. Mbcap (talk) 00:29, 27 April 2015 (UTC)[reply]
Oppose per above and per WP:COMMONNAME, Plus "Huntington's Disease" sounds more normal than "Huntington Disease". –Davey2010^Talk 19:22, 27 April 2015 (UTC)[reply]
Oppose per WP:COMMONNAME. -- Necrothesp (talk) 13:41, 29 April 2015 (UTC)[reply]

The above discussion is preserved as an archive of a requested move. Please do not modify it. Subsequent comments should be made in a new section on this talk page or in a move review. No further edits should be made to this section.

Caffeine

better source proposed Dubbin^{u | t | c} 18:24, 13 June 2016 (UTC)[reply]

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With respect to this content "An association between caffeine intake and age of onset in Huntington disease has been found, with earlier onset of about 4 years among patients consuming more than 190 mg caffeine per day compared to those who consumed less than 190 mg per day.Simonin, C.; Duru, C.; Salleron, J.; Hincker, P.; Charles, P.; Delval, A.; Youssov, K.; Burnouf, S.; Azulay, J.-P.; Verny, C.; Scherer, C.; Tranchant, C.; Goizet, C.; Debruxelles, S.; Defebvre, L.; Sablonnière, B.; Romon-Rousseaux, M.; Buée, L.; Destée, A.; Godefroy, O.; Dürr, A.; Landwehrmeyer, B.; Bachoud-Levi, A.-C.; Richard, F.; Blum, D.; Krystkowiak, P. (2013), "Association between caffeine intake and age at onset in Huntington's disease", Neurobiology of Disease, 58 (0): 179–182, doi:10.1016/j.nbd.2013.05.013{{citation}}: CS1 maint: multiple names: authors list (link) Caffeine is an adenosine receptor antagonist and adenosine receptors are believed to have an important role in Huntington. http://www.ncbi.nlm.nih.gov/pubmed/25175968"

This first ref is a primary source [6]

The second is a review [7] which we should simply use instead. Have formatted it appropriately and combined it into the rest of the treatment section. Doc James (talk · contribs · email) 17:26, 9 July 2015 (UTC)[reply]

As per WP:MEDRS "A primary source may be presented adjunctively to a secondary source". I put it this way but it was changed back by Sminthopsis84 when he edited the text. User:User931 20:37, 9 July 2015 (UTC)[reply]

Per this ref [8] I took "positively associated" to mean later onset rather than earlier onset as later onset would be positive.

Have looked at the full text and realize that I was wrong. It should have been "Higher levels of caffeine intake is related to a earlier onset of Huntington's." Doc James (talk · contribs · email) 19:42, 9 July 2015 (UTC)[reply]

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Recent edits

consensus Dubbin^{u | t | c} 18:24, 13 June 2016 (UTC)[reply]

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This article has received substantial editing over the last few days, and some of the changes don't strike me as appropriate. In particular, material about ongoing clinical trials, which is primary-sourced and is bound to "time out" pretty soon. I would favor sticking to the MEDRS-based approach of relying entirely on secondary sources to the full extent possible. Looie496 (talk) 14:03, 11 July 2015 (UTC)[reply]

I agree completely and have removed the speculative material. We should not be reporting planned trials. I suspect someone with a connection to the SIGNAL trial is adding these mentions. It is a small trial of a strange agent with only one mouse trial (in which the statistics don't show significant benefit of treated vs untreated transgenic animals) to support its use in HD. It certainly doesn't belong on this wikipedia page until its results are published in a MEDRS journal. Dubbin^{u | t | c} 08:53, 13 July 2015 (UTC)[reply]

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Request for Edit

not yet mentioned in suitable independent WP:MEDRS source Dubbin^{u | t | c} 18:24, 13 June 2016 (UTC)[reply]

The following discussion is closed. Please do not modify it. Subsequent comments should be made on the appropriate discussion page. No further edits should be made to this discussion.

Apologies for improper formatting in advance - this is my very first time posting on a talk page. I propose adding the following text to the Mechanism section:

"Depletion of the enzyme cystathionine γ-lyase (CSE) may also influence the deurodegenerative pathophysiology of HD. Evidence points to a reduction in CSE gene transcription—this is hypothesized to be a result of interactions between mHTT and specificity protein 1 (Sp1). Reference:Paul BD, Sbodio JI, Xu R, Vandiver MS, Cha JY, Snowman AM, Snyder SH (2014). "Cystathionine γ-lyase Deficiency Mediates Neurodegeneration in Huntington's Disease". Nature. 509 (7498): 96–100. doi:10.1038/nature13136. PMC 4349202. PMID 24670645.{{cite journal}}: CS1 maint: multiple names: authors list (link) Sp1 is a transcriptional activator for CSE."

Reasons

Source is open-access, and is actually by the same group referenced a couple sentences earlier
Findings are significant in that they point to a putative non-mHTT pathology

— Preceding unsigned comment added by SaeJunHwan (talk • contribs)

Response

I moved your request to the bottom of the talk page which is where new topics are added. The paper you suggest is not appropriate for addition because it is a primary research article. New research needs to be backed up by sources consistent with WP:MEDRS, the Wikipedia guide to identifying reliable sources for medical articles. Essentially, secondary sources (e.g. high-quality review articles) should be used, and single sources such as the one you suggest are best avoided. This is because wikipedia should present scientific consensus, not showcase novel findings that have yet to be replicated.

People who suggest the addition of specific articles often have a personal or professional connection to the lab or the research. I'm not suggesting you do, but please make yourself aware of WP:COI, Wikipedia's policy on conflict of interest.Dubbin^{u | t | c} 12:55, 9 March 2016 (UTC)[reply]

Response to Response

Thank you for moving my request!

I believe that I fully understand both WP:MEDRS and WP:COI. However, I still believe that this information is appropriate. Let me assure you that there is no COI—I can only wish to be in a place as seemingly amazing as the Snyder lab!

As you know, WP:MEDRS does not require secondary sources, and though it does strongly discourage the use of primary literature, it provides for its use. Therefore, the statement "the paper...is not appropriate...because it is a primary research article" is not true. There must be something else in addition to the primary-ness, to make the primary research not worthy of inclusion.

The additional information that I am advocating meets WP:MEDRS guidelines and merits inclusion as follows:

The information is not clinically relevant—a reasonable person would not attempt to obtain treatment based on the information, as it is 1) not presented in context of a therapy 2) not suggested as being relevant to therapy
The information has not been found controversial in the scientific community
The information does not contradict or refute other findings presented in the WP article. It does not cause confusion.
The paragraph is worded in a way that shows the evidence is still under investigation: "may", "points to" and "hypothesized"
The information gives an example of an "identified" pathological pathway listed in the fourth paragraph of the Mechanism section—i.e., effects on the expression of genes.

Weaker reasons for inclusion are:

Reference 30 is a primary research article, yet is being used twice
The proposed article has been referenced 18 times
The proposed article is over a year old
The Dr. Snyder is one of (if not the) most cited and respected biologists and neuroscientists on the planet. That is not an exaggeration.

It is important to remember that, in addition to being a widely used source of health information WP is also used as a resource/launching-point for persons researching various topics. It it therefore vital that WP contain the most up-to-date reliable information.

I look forward to your response. SaeJunHwan (talk) 19:59, 29 March 2016 (UTC)[reply]

Question

Isn't the same point covered adequately by the review at PMC 4307159? Perhaps some subtle rewording might be needed, but that's not a major obstacle.LeadSongDog come howl! 16:33, 30 March 2016 (UTC)[reply]

Response to Question

Yes, the article does adequately cover the topic. Rewording is not an obstacle at all - this is WP! Great job resolving an issue!

I propose the following be added:

Depletion of the enzyme cystathionine γ-lyase (CSE) may also influence the neurodegenerative pathophysiology of HD. Evidence points to a reduction in CSE gene transcription—this is hypothesized to be a result of interactions between mHTT and specificity protein 1 (Sp1). Sp1 is a transcriptional activator for CSE. Reference:Paul BD, Snyder SH (2015). "Modes of Physiologic H2S Signaling in the Brain and Peripheral Tissues". Antioxidants & Redox Signaling. 22 (5): 411–423. doi:10.1089/ars.2014.5917. PMC 4307159. PMID 24684551.

SaeJunHwan (talk) 17:31, 30 March 2016 (UTC)[reply]

I disagree. The review is written by the same lab that produced the original publication. It cannot be considered any differently from the original, unreplicated finding. Your admiration for Snyder aside, there is nothing special about this particular single publication that sets it apart from any of a hundred others that could be included but aren't because they haven't been replicated. 18 citations isn't very many, and a year isn't very long in neuroscience. Even the biggest names can publish findings that do not stand the test of replication or time. The absence of authoritative independent reviews here cannot be taken as evidence that the finding is 'uncontroversial' - it is in fact very controversial in the field. But it takes time for others to run experiments that would replicate or refute it and then get them published. In the meantime it is not Wikipedia's job to showcase individual findings like this. Wikipedia is not a newspaper and Wikipedia is not a crystal ball - its purpose is not to showcase the latest findings, nor to predict what will be thought important in the future. These principles are especially true of featured articles like this, which are maintained according to the strictest standards. It is always best to wait until the field has given proper consideration to novel findings. Meanwhile, if you think there is content or citations that do not meet WP:MEDRS criteria, feel free to propose edits or deletions. Dubbin^{u | t | c} 12:48, 31 March 2016 (UTC)[reply]

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[GoodenoughLevine1974-1] Ursula Goodenough; Robert Paul Levine (1 January 1974). Genetics. Holt, Rinehart and Winston. p. 531. ISBN 978-0-03-084490-4.

[McKusick1972-2] Victor A McKusick (December 1972). "Human Chromosome Mapping Newsletter" (PDF). {{cite journal}}: Cite journal requires |journal= (help)

[3] Keenan, Karen (6th). "How Do Partners Find Out About the Risk of Huntington's Disease in Couple Relationships?". National Society of Genetic Counselors, Inc 2013. {{cite journal}}: Check date values in: |date= and |year= / |date= mismatch (help); Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)

[1]

[2]

[1]

A quibble concerning the lead

last minute changes in history section

External Review Comments

Gene and Protein nomenclature

Introduction

Diagnosis

Differential Diagnosis

Prognosis

Epidemiology

Society and culture

Fatal?

On penetrance

Creation of the HDF

HD category

On ethics

expansion of aggregate function

References layout

Claim of "first autosomal disease locus found using genetic linkage analysis"

Inadequacy of dmoz for external links

Name

Proposed external links

Major support organizations

Scientific resources for lay readers

Major research organizations

Research directions

Caspase-6 cleavage of mHtt

New link (HDYO)

Diagnosis

Bravo, thank you for quality, continuing improvements.

GM1 and HD

Recent additions with some problems in sourcing

Research directions: glycemic control

Requested move 23 April 2015

Caffeine

Recent edits

Request for Edit

Reasons

Response

Response to Response

Question

Response to Question