Talk:Huntington's disease/Archive 1

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[edit] First gene

"..this is the first time a specific gene is linked to a medical condition." In 1983? I don't think so. The HPRT/Lesch-Nyhan Syndrome was confirmed in 1975. I have an old medical genetics text from 1977 that states albinism "is absence of tyrosinase, or if present its failure to function." I happen to have a 1983 edition of McKusick's Mendelian Inheritance in Man. It lists several specific genes for genetic disease, admittedly mostly on the X chromosome or dominant.

I've taken out the statement. Ted 22:56, 15 April 2006 (UTC)

Maybe it was the first pre-symptomatic gene? Can't find the information at present.

Leevanjackson 23:36, 15 April 2006 (UTC)

The albinism comment is irrelevant, no-one knew where the gene was located, all they knew was that there was an abnormal enzyme in a cell. In the case of Gusella et al, it was the first time that the DNA marker for a defective gene was found, and the work was done on samples from the large poulation of HD sufferers in Venezuela. "Linkage Information. The finding (KanandDozy,1978) and elaboration into doctrine (Botsteinetal., 1980) that DNA polymorphisms (then, restriction fragment linkage polymorphisms, or RFLPs; now,single nucleotide polymorphisms, or SNPs) could be followed as Mendelian alleles in pedigrees led to a great expansion of the density of genetic maps in all organisms so studied. The ability to find such systematically and unambiguously scorable markers linked to inherited traits allowed isolation of genes responsible for these traits (the first being for that for Huntington’s chorea [Gusella et al., 1983]) by DNA walking (Benderetal.,1983). Most human medical genetics still depends on isolation of individual disease genes by this tactic." Brent R, Genomic Biology, Review. Cell, Vol.100,169–183, January7, 2000. Note that this was not the identification of the gene itself, nor of the sequence causing the defect. That came in 1993: "The Huntington's disease (HD) gene has been mapped in 4p16.3 but has eluded identification. We have used haplotype analysis of linkage disequilibrium to spotlight a small segment of 4p16.3 as the likely location of the defect. A new gene, IT15, isolated using cloned trapped exons from the target area contains a polymorphic trinucleotide repeat that is expanded and unstable on HD chromosomes. A (CAG)n repeat longer than the normal range was observed on HD chromosomes from all 75 disease families examined, comprising a variety of ethnic backgrounds and 4p16.3 haplotypes. The (CAG)n repeat appears to be located within the coding sequence of a predicted approximately 348 kd protein that is widely expressed but unrelated to any known gene. Thus, the HD mutation involves an unstable DNA segment, similar to those described in fragile X syndrome, spino-bulbar muscular atrophy, and myotonic dystrophy, acting in the context of a novel 4p16.3 gene to produce a dominant phenotype." Huntington's Disease Collaborative Research Group. A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. Cell 72:971-83 (1993). --Seejyb 22:16, 19 July 2006 (UTC)

[edit] rejigging headings and order

I am just about to chamge the order of the article to fit the medical template see http://en.wikipedia.org/wiki/Wikipedia:WikiProject_Clinical_medicine/Template_for_medical_conditions no content changes just the sectionsLeevanjackson 12:49, 17 April 2006 (UTC)

The template is not particularly designed for genetic conditions/syndromes. For Huntington's disease, the genetics should be a main heading. Good luck with the project. Ted 12:58, 17 April 2006 (UTC)

For whatever reason, I'm currently watching three genetic diseases/syndrome: Huntington's disease, Turner syndrome, and Down syndrome. Huntington's disease and Down syndrome have History as the first section after the introduction. For Turner syndrome, it is still fairly early. I'm not sure why; just thought I would throw that out. Ted 13:02, 17 April 2006 (UTC)

Thankyou Ted, I'm done for now, the order and headings largley comply now. Your cight about genetics, have left it as a main heading. As for history coming first - it did seem _right_ there, but now its in the style we can see if the style needs changing for conditions etc. well done on all your rc patrols :) Leevanjackson 13:27, 17 April 2006 (UTC)

[edit] George Huntington

The intro reads "Ohio physician George Huntington..." but later on in the article it says "George Huntington was one of three generations of medical practitioners in Long Island." Can we clear this up? Akno21 21:03, 05 May 2006 (UTC)

He grew up on Long Island and did all of his observations concerning Huntington disease while observing his father & grandfather's practice. He was a country practioner in Ohio when he first presented his findings. Both statements are probably technically correct, although I don't believe he practiced medicine in New York (or not for long if he did). Ted 01:27, 6 May 2006 (UTC)

a bit more depth is found, http://www.uic.edu/depts/mcne/founders/page0048.html Leevanjackson 11:12, 7 May 2006 (UTC)

The statement is misleading, misrepresenting both the life work of Huntington and the place where all the research was done. Huntington can no more be called an "Ohio physician" than a Japanese doctor from Tokio, who has done all his research and prepared his paper in Tokio, but read the paper while he was studying in New York for 2 years, before going back to spend the rest of his life in Tokio, can be called a "New York" physician.

From Stevenson, Charles S. A Biography of George Huntington, M.D. Bulletin Of The Institute Of The History Of Medicine, The Johns Hopkins University. Ed Henry E. Sigerist, Vol II, Number 2, April, 1934: Huntington was born and grew up in East Hampton, New York, where his father and grandfather had practiced as family physicians. "[He]... graduated from the College of Physicians and Surgeons of Columbia University, New York, in the Spring of 1871. ... during the Summer and Fall of 1871 he made notes preliminary to writing a paper on chorea. He finally wrote out the original draft of his essay and it was carefully revised by his father, whose pencil notes and corrections are seen today on the original manuscript. Late in 1871, young Dr. Huntington went to Pomeroy, Ohio... He took his unpublished article with him, and on February 15, 1872, he read it before the Meigs and Mason Academy of Medicine at Middleport, Ohio. Here it was well received, and so he sent it to the editors of the Medical and Surgical Reporter of Philadelphia, and it was published in this journal in the issue of April 13, 1872. Early in 1782, young Dr. Huntington met Miss Mary Elizabeth Hackard, the daughter of Judge Martin Hackard of Pomeroy. He was struck by her charm, intelligence, and energy, and thus followed a two year courtship, which culminated with their marriage in 1874. By this time the young Doctor had come to realize that Pomeroy was abundantly supplied with physicians, and that the chance for successful competition seemed small, so he took his young bride back to East Hampton with him. It was about this time that he began to suffer from severe attacks of spasmodic asthma, and this disease was gradually to become a more and more important factor in his life. After a few months stay in his native town, the young couple decided that it would be best for them to move to La Grangeville, which is in Dutchess County in the Catskill Mountains of New York. There they were to try their fortunes in life. Accordingly, in the Fall of 1874, they arrived at this town, and the local residents soon began to come with their troubles to the home where hung the bright new sign "George Huntington, M.D." --Seejyb 22:31, 19 July 2006 (UTC)

[edit] Clinical trials - no there aren't 100 current and 300 total!

Can someone fix this? If you look at the reference, there are only 9 studies involving HD which are still recruiting and 19 total. The other studies have nothing to do with HD. There have been very few Phase III clinical trials in HD. The only two in the last decade were CoQ10 and remacemide (CARE-HD) and ethyl-EPA (Miraxion).

The search in the text was picking up the location huntington too, will fix Leevanjackson 11:19, 12 May 2006 (UTC)

[edit] Image

I don't think the image is really appropriate. A much better choice would be a photo of George Huntington or something related to huntingtin protein (an IHC pic could be nice, for example). Peter Z.Talk 00:34, 19 June 2006 (UTC)

Why does the image say "your mom" ? 89.233.225.126 23:52, 10 January 2007 (UTC)

[edit] Age of onset

"The mean age of onset is 35 to 44 years." references: Hayden M. Huntington's Chorea. Springer-Verlag, Berlin, (1981). and Harper P S. Huntington Disease. WB Saunders, London, (1996)


In response to the quote: "These physical symptoms commonly become noticeable in a person's forties[citation needed], but can occur at any age." A quote from Thompson & Thompson Genetics in Medicine (2007) "The patient's age of disease onset is inversely proportional to the number of HD CAG repeats." pg. 276

I'm no good at citing sources, so here is a to the amazon page with the book: [1] —The preceding unsigned comment was added by 151.197.226.243 (talk) 04:27:33, August 19, 2007 (UTC)

[edit] Management of HD

I will post my proposed rewrite tomorrow. Meanwhile note that Haydon et al (in Cell, 2006) could prevent the development of HD in experimental transgenic mice by further mutating the HD gene so that it was resistant to caspase-6, and this mutated-mutated huntingtin, which does not exist in humans at all, did not cause HD in the mice. They deduce that it is the non-breakdown of mutated-mutated huntingtin by this enzyme that prevented HD-like disease in the mice. The inference is that an inhibitor of caspase-6 may prevent HD in humans, but that is far from reality at this stage. The only thing one can say is that inhibition of caspase-6 may prevent the development of HD in humans with "ordinary" mutated huntingtin. What the other effects would be, e.g. since now no cells would be able to utilise caspase-6, is much too early to say. Yet it is good work, and as some-one said, "ground breaking". --Seejyb 22:59, 19 July 2006 (UTC)


The section citing that "Calorie restriction" may postpone onset in HD: ["A calorie restrictive diet delays the onset of symptoms in HD mice.[8]"] is strongly misleading and is opposite the observations in people where weight loss is related to more rapid disease progression. Such as for example the article "Myers RH, Sax DS, Koroshetz WJ, Mastromauro CA, Cupples LA, Kiely DK, Pettengill FK, Bird ED. Factors associated with slow progression in Huntington's disease. Archives of Neurology, 1991;48:800-804." 155.41.190.45 17:33, 31 August 2006 (UTC)–—RMyers

[edit] Famous patients?

Is there room (and relevance) for a section on current and historical famous people with Huntington's? MIP | Talk 09:17, 24 July 2006 (UTC)

  • there was a section before, but it was incorporated into the history and organisation sections ( woodie guthrie and wexlar). Are there any others you were thinking of in particular? Leevanjackson 11:48, 24 July 2006 (UTC)
I was wondering if there are any retrospective diagnoses that we know of. (By retrospective diagnoses, I refer to situations akin to the academic suggestion that porphyria might have been the cause of George III's 'madness'.)
possibly witch trials amongst them the salem witch trials Leevanjackson 16:47, 24 July 2006 (UTC)
Now that you mention it, I remember reading an article, once, which mentioned Salem and the suggestion of HD or Ergotism. IIRC that article also had some other notables with suspected HD. I'll try to find it again. MIP | Talk 16:59, 24 July 2006 (UTC)

If you do this, I strongly suggest making a separate page for famous patients, and only allow additions with a strong citation. Otherwise, it can quickly degenerate to WP:OR. Sandy has done a great job with this on the Tourette syndrome page (see Sociological_and_cultural_aspects_of_Tourette_syndrome#Notable_individuals). TedTalk/Contributions 02:25, 25 July 2006 (UTC)

Definitely! When writing something 'from scratch', I usually only choose medical references that are indexed in Medline or published in a speciality reference-book, due to habits created when preparing articles for publication.
I've noticed that many medical articles in Wikipedia have lists of historical figures who speculatively might have had a certain condition, with the same figure often appearing in several lists, as a result of this. Einstein alone is mentioned in at least HA-ADD, Autism, Asperger's and even as dyslexic in the Einstein page. MIP | Talk 13:27, 25 July 2006 (UTC)
Thank you for the kind words, Ted. I had *such* a problem with speculative edits (George W. Bush has TS, dontya know?) before I extensively referenced the notables, and moved them to a separate article, and I've had no problems with speculative edits since. I should mention that the idea came from the very notable Wikiphysician, encephalon. Sandy 13:37, 25 July 2006 (UTC)

[edit] British vs American English

This should be more consistent. I'm not working on this, so I won't make a decision as to which one should be used, but it should be more consistent. I can help convert it once that has been decided. TedTalk/Contributions 19:19, 30 July 2006 (UTC)

I don't know why people believe that everything has to be one or the other. Give credit to the people who wrote it by retaining their spelling. - Samsara (talk • contribs) 22:19, 30 July 2006 (UTC)
It seems less professional to me, although I suppose I shouldn't be worried about professionalism in Wikipedia, anyway. I fail to see how it gives credit to the original writers ("See the 's'? That's mine!), but OK. It really isn't a big deal. I'll withdraw my suggestion. TedTalk/Contributions 01:48, 31 July 2006 (UTC)

[edit] Article rating

Should it be a GA or an FA candidate? NCurse Image:Edu science.png work 11:59, 7 August 2006 (UTC)

I don't believe it is ready for FA. In my experience, GA is useless as a way to improve the article. I'd suggest review first. Those are quite variable, but if we are lucky, the comments will lead to an improved article. TedTalk/Contributions 11:05, 10 August 2006 (UTC)

[edit] Introduction

I'm no expert, but the introduction seems to have quite a bit of info that doesn't really belong in the introduction. Thoughts? Aaadddaaammm 08:56, 30 August 2006 (UTC)

The peer review suggestions were:At least it should mention that the trinucleotide repeat leads to a polyglutamine region in the huntingtin protein; the prevalence of the disease; the most common/characteristic symptoms; and the fact that it is not curable.

This was in addition to some synonyms, a history of its naming ( george Huntington ), a brief overview of the disease mechanism, the age of onset.

I think maybe the naming could be moved into the history sectio, but the picture of George Huntington would have top be replaced by a more descriptive image - any ideas, maybe the huntingtin protein diagram? Leevanjackson 11:20, 30 August 2006 (UTC)
I don't think the length of the intro is a problem. Looking at the other eponymous diseases, the standard seems to be to list the person honored in the intro. Possibly spliting it into two paragraphs or three paragraphs would help, avoiding a "list-y" introduction. I believe the wiki-standard for an article of this length is 2-3 paragraphs. Does the age of onset really have a Gaussian (capitalized since it is named after Gauss) distribution? I had thought it was not symmetrical.
On a more philosophical point, no genetic disorder is curable (to date). Some are manageable, such as PKU. Many (most?) are not. Of course, the readers of the encyclopedia are not expected to understand that. TedTalk/Contributions 12:26, 30 August 2006 (UTC)
OK if you want to get philosophical, we can. Some genetic diseases are curable. Cancer is a genetic disease. It may not usually be an inherited disease, but the cause of cancer is invariably genetic. You could also argue that gene therapy for SCID has cured this genetic disease. Admittedly, the germ line will still carry the genetic disease, and the cure has significant side effects (cancer) but it's still effectively a cure. Aaadddaaammm 07:29, 16 October 2006 (UTC)


[edit] Testing Price

The article states the test for determining if a person carries the extra GAC pattern is "tens of thousands" of dollars. Actually, this test is now a few hundred dollars, at most. This is in 2007 dollars. I think the article should be updated. —The preceding unsigned comment was added by 68.4.70.65 (talk) 07:08, 18 March 2007 (UTC).


No, the article is accurate. While the usual gene test itself is only a few hundred dollars (I know, I've done it), the price for embryonic genetic screening and in vitro fertilization, the only way to be sure an at-risk parent does not carry a gene-positive child to term, is still very high. (And it's CAG, not GAC.) —Preceding unsigned comment added by 65.127.122.226 (talk) 14:54, 25 October 2007 (UTC)

[edit] Minor edit

I was just here reading and learning. I am writing up a meeting on HD and needed some background. But the bit about the N terminal end was confusing me, so I edited slightly to say that the N-terminal end of the protein and the CAG repeat end of the gene are the same. I assume that's correct. If not, say what it is! Because it was unclear. Also, there was an entry about mice knockins that only had the first exon, but the sentence didn't say it was in mice, so I edited that.

Lastly, I think the last paragraph about the Cell paper results needs to be rewritten in the style of the rest of the article, as it reads now like a Merck press release. I'm sure it was very exciting when it first came out, but it's taking up too much space at this point.

I'd do it myself, but I have to get back to this proceedings, which, by the way, involves more advances on HD. If I don't get back here, please look at the work of Robert Schwarcz, of the Maryland Psychiatric Research Center.

This article is so long and more info is coming. Have you considered splitting it up, so there's a general article, on history and disovery of gene, symptoms, etc, and then a more technical one focused on the mechanism and current research to find a treatment for HD? So much information is being generated by the work of the various HD foundations. Together, they are pumping about $80 milllion a year into research on this one disease. Maybe more. All that information isn't going to fit here.... Eperotao 14:44, 28 March 2007 (UTC)

[edit] Mechanism

D666D 22:35, 26 September 2007 (UTC) Any one want to bet that this section was written by one of the authors of the Cell article mentioned, a fan of Dr. Marian DiFiglia, or, more likely, a member of the Merck press team? While this work maybe excelent and highly important, caspase activity can not be the full story of the mechanism(s). Points for discussion should include: excitotoxicity (including NMDA); neurotrophic factors (including BDNF); axonal transport; transcription/translslation; neuronal context (why do some neurones undergo degeneration, while others don't, despite mutant huntingtin being expressed in EVERY cell; synaptic transmission; interneuronal inclusions (whether they may be neurotoxic or neuroprotective may still be unclear; but a discussion of how they may potentially be harmful should be included); Proteosomal overload.

have moved reworked into line with rest of section Leevanjackson 22:10, 13 November 2007 (UTC)