Huntington's Disease--A Review (original) (raw)
Related papers
Huntington disease--another chapter rewritten
American journal of human genetics, 1996
To those of us who began life when humans had 48 chromosomes and who began working in genetics when the (by then 46) chromosomes had no bands and chromosome 4 could not reliably be distinguished from chromosome 5, the mere ability to diagnose and correlate the clinical phenotypes of genetic disorders with their molecular genotypes is a source of continuing astonishment and pleasure. Indeed, molecular genetic analysis of neurogenetic disorders such as Huntington disease (HD) has provided a steady stream of challenges and surprises to all who believe the genetic principles that they were taught about these disorders. The paper by Rubinsztein et al. in this issue of the journal highlights yet another surprise, which was adumbrated even in the initial paper announcing the discovery of the HD gene: incomplete penetrance of HD gene mutations.
investigators of the European Huntington's Disease Network¶, Ana M. Zubiaga1
2016
Age of onset (AO) of Huntington disease (HD) is mainly determined by the length of the CAG repeat expansion (CAGexp) in exon 1 of theHTT gene. Additional genetic variation has been suggested to contribute to AO, although the mechanism by which it could affect AO is pres-ently unknown. The aim of this study is to explore the contribution of candidate genetic factors to HD AO in order to gain insight into the pathogenic mechanisms underlying this disorder. For that purpose, two AO definitions were used: the earliest age with unequivocal signs of HD (ear-liest AO or eAO), and the first motor symptoms age (motor AO or mAO). Multiple linear regres-sion analyses were performed between genetic variation within 20 candidate genes and eAO or mAO, using DNA and clinical information of 253 HD patients from REGISTRY project. Gene
Natural history of Huntington disease
JAMA neurology, 2013
Understanding the natural history of Huntington disease will inform patients and clinicians on the disease course and researchers on the design of clinical trials. To determine the longitudinal change in clinical features among individuals with Huntington disease compared with controls. Prospective, longitudinal cohort study at 44 research sites in Australia (n = 2), Canada (n =4), and the United States (n = 38). Three hundred thirty-four individuals with clinically manifest Huntington disease who had at least 3 years of annually accrued longitudinal data and 142 controls consisting of caregivers and spouses who had no genetic risk of Huntington disease. Change in movement, cognition, behavior, and function as measured by the Unified Huntington's Disease Rating Scale, the Mini-Mental State Examination, and vital signs. Total motor score worsened by 3.0 points (95% CI, 2.5-3.4) per year and chorea worsened by 0.3 point per year (95% CI, 0.1-0.5). Cognition declined by 0.7 point (...
Huntington disease: DNA analysis in brazilian population
Arquivos de Neuro-Psiquiatria, 2000
Huntington disease (HD) is associated with expansions of a CAG trinucleotide repeat in the HD gene. Accurate measurement of a specific CAG repeat sequence in the HD gene in 92 Brazilian controls without HD, 44 Brazilian subjects with clinical findings suggestive of HD and 40 individuals from 6 putative HD families, showed a range from 7 to 33 repeats in normal subjects and 39 to 88 repeats in affected subjects. A trend between early age at onset of first symptoms and increasing number of repeats was seen. Major increase of repeat size through paternal inheritance than through maternal inheritance was observed. Data generated from this study may have significant implications for the etiology, knowledge of the incidence, diagnosis, prognosis, genetic counseling and treatment of HD Brazilian patients.
The Lancet, 2007
Search strategy and selection criteria I searched Pub Med from 1965-2005 for the term "Huntington's Disease" cross referenced with the terms "apoptosis", "axonal transport", "mitochondria", "animal model", "proteosome", "transcription", "juvenile", "suicide", "neurotransmitters", "age of onset", "identical twins", "neurodegeneration", and "imaging". I translated all non-English language publications that resulted from this search strategy. I mainly selected articles from the past fi ve years, but did not exclude commonly referenced and highly regarded older publications. I also searched the reference lists of articles identifi ed by this search strategy and selected those that I judged relevant. Several review articles and book chapters were included because they provide comprehensive overviews beyond the scope of this Seminar. The reference list was further modifi ed during the peer-review process based on comments from the reviewers. Year Event Publications (n)* 1374 Epidemic dancing mania described .. 1500 Paracelsus suggests CNS origin for chorea .. 1686 Thomas Sydenham describes post-infectious chorea .. 1832 John Elliotson identifi es inherited form of chorea 1 .. 1872 George Huntington characterises Huntington's disease 5 ..
Molecular analysis of late onset Huntington's disease
Journal of Medical Genetics, 1993
Late onset Huntington's disease is characterised by onset of symptoms after the age of 50 and is usually associated with a milder course. We have analysed the CAG trinucleotide repeat within the HD gene in 133 late onset patients from 107 extended families. The median upper allele size for the CAG repeat was 42 with a range of 38 to 48 repeats. A significant negative correlation (r = -0-29, p = 0 001) was found between the length of repeat and age of onset for the total cohort. However, for persons with age of onset greater than 60, no significant correlation was found. In addition, no significant correlation was found between age of onset and size of the lower allele and the sex of the affected parent or grandparent. There was no preponderance of maternal descent for late onset cases in this series. This study shows that variation in repeat length only accounts for approximately 7% of the variation in age of onset for persons beyond the age of 50 and clearly shows how with increasing onset age the effect of the repeat length on this onset age seems to diminish. (J Med Genet 1993;30:991-5)
New mutation to Huntington's disease
Journal of Medical Genetics, 1989
We report a large family with an isolated case of Huntington's disease (HD), which is probably the result of a new mutation. The patient developed clinical signs typical of HD at the age of 36. The clinical course of the patient's disease is documented by several clinical admissions over a period of 14 years at present. The family history is strikingly negative with the parents having been clearly unaffected into their 80s and with 13 older and two younger, living, healthy sibs. Extensive testing of polymorphic markers (blood groups, red cell and serum proteins, HLA antigens) showed no indication of non-paternity, but rather gave strong support to the hypothesis that the proband is a full sib. In addition, DNA typing for several RFLPs known to be closely linked to the HD gene locus indicated that several clearly unaffected sibs share one or the other or both of the patient's haplotypes. This is further evidence in favour of the hypothesis of a new mutation at the HD locus.