title: Huntington's disease genetics.
abstract: Huntington's disease (HD) is a dominantly transmitted neurodegenerative disorder with wide variation in onset age but with an average age at onset of 40 years. Children of HD gene carriers have a 50% chance of inheriting the disease. The characteristic symptoms of HD are involuntary choreiform movements, cognitive impairment, mood disorders, and behavioral changes which are chronic and progressive over the course of the illness. HD is a "trinucleotide repeat" disorder, which is caused by an increase in the number of CAG repeats in the HD gene. Repeats of 40 or larger are associated with disease expression, whereas repeats of 26 and smaller are normal. Intermediate numbers of repeats, between 27 and 35, are not associated with disease expression but may expand in paternal transmission, resulting in the disease in descendents. Repeats of 36-39 are associated with reduced penetrance whereby some develop HD and others do not. The identification of the genetic defect in HD permits direct genetic testing for the presence of the gene alteration responsible for the disease. Tests may be performed in three circumstances: (1) confirmation of diagnosis, (2) predictive testing of persons at genetic risk for inheriting HD, and (3) prenatal testing. Testing is widely available and much experience has been gained with protocols that assist the individual in making an informed choice about test options, and minimize the occurrence of adverse emotional outcomes.
authors.affiliation: Department of Neurology, Boston University School of Medicine, Boston, Massachusetts 02118, USA. rmyers@bu.edu
authors.forename: Richard H
authors.initials: RH
authors.lastname: Myers
mesh_terms: D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000175:diagnosis / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D018911:Trinucleotide Repeats
chemical_list: C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins
references.citation: J Med Genet. 2001 Apr;38(4):E12
references.pmid: 11283208
references.citation: Am J Hum Genet. 1999 May;64(5):1293-304
references.pmid: 10205260
references.citation: Clin Genet. 2001 Sep;60(3):198-205
references.pmid: 11595021
references.citation: Genet Test. 2001 Fall;5(3):213-8
references.pmid: 11788086
references.citation: Free Radic Res. 2002 Apr;36(4):455-60
references.pmid: 12069110
references.citation: Prenat Diagn. 2002 Jun;22(6):503-7
references.pmid: 12116316
references.citation: Clin Obstet Gynecol. 2002 Sep;45(3):640-8; discussion 730-2
references.pmid: 12370603
references.citation: Neuron. 2002 Aug 29;35(5):819-22
references.pmid: 12372277
references.citation: Fertil Steril. 2003 Jan;79(1):81-90
references.pmid: 12524068
references.citation: Lancet. 2003 May 10;361(9369):1642-4
references.pmid: 12747895
references.citation: Am J Med Genet A. 2003 Jun 15;119A(3):279-82
references.pmid: 12784292
references.citation: Am J Hum Genet. 2003 Sep;73(3):682-7
references.pmid: 12900792
references.citation: Nature. 1983 Nov 17-23;306(5940):234-8
references.pmid: 6316146
references.citation: J Neurol Neurosurg Psychiatry. 1984 Dec;47(12):1283-7
references.pmid: 6239910
references.citation: Am J Med Genet. 1986 Jun;24(2):305-11
references.pmid: 2940862
references.citation: Br J Psychiatry. 1992 Oct;161:481-8
references.pmid: 1393334
references.citation: Cell. 1993 Mar 26;72(6):971-83
references.pmid: 8458085
references.citation: Nat Genet. 1993 Aug;4(4):387-92
references.pmid: 8401587
references.citation: Hum Mol Genet. 1993 Dec;2(12):2063-7
references.pmid: 8111374
references.citation: Neurology. 1994 Aug;44(8):1369-73
references.pmid: 7914682
references.citation: Neurology. 1994 Aug;44(8):1533-6
references.pmid: 8058167
references.citation: Am J Hum Genet. 1995 Sep;57(3):593-602
references.pmid: 7668287
references.citation: Hum Mol Genet. 1997 Feb;6(2):301-9
references.pmid: 9063751
references.citation: Am J Med Genet. 1997 Jun 27;70(4):365-70
references.pmid: 9182776
references.citation: Am J Med Genet. 2001 Jul 8;105(5):399-403
references.pmid: 11449389