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Huntington's disease–like 2 (HDL2) in North America and Japan
Author(s) -
Margolis Russell L.,
Holmes Susan E.,
Rosenblatt Adam,
Gourley Lisa,
O'Hearn Elizabeth,
Ross Christopher A.,
Seltzer William K.,
Walker Ruth H.,
Ashizawa Tetsuo,
Rasmussen Astrid,
Hayden Michael,
Almqvist Elisabeth W.,
Harris Juliette,
Fahn Stanley,
MacDonald Marcy E.,
Mysore Jayalakshmi,
Shimohata Takayoshi,
Tsuji Shoji,
Potter Nicholas,
Nakaso Kazuhiro,
Adachi Yoshiki,
Nakashima Kenji,
Bird Thomas,
Krause Amanda,
Greenstein Penny
Publication year - 2004
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.20248
Subject(s) - huntington's disease , disease , medicine , gerontology
Huntington's Disease–like 2 (HDL2) is a progressive, autosomal dominant, neurodegenerative disorder with marked clinical and pathological similarities to Huntington's disease (HD). The causal mutation is a CTG/CAG expansion mutation on chromosome 16q24.3, in a variably spliced exon of junctophilin‐3. The frequency of HDL2 was determined in nine independent series of patients referred for HD testing or selected for the presence of an HD‐like phenotype in North America or Japan. The repeat length, ancestry, and age of onset of all North American HDL2 cases were determined. The results show that HDL2 is very rare, with a frequency of 0 to 15% among patients in the nine case series with an HD‐like presentation who do not have the HD mutation. HDL2 is predominantly, and perhaps exclusively, found in individuals of African ancestry. Repeat expansions ranged from 44 to 57 triplets, with length instability in maternal transmission detected in a repeat of 33 triplets. A younger age of onset is correlated with a longer repeat length ( r 2 = 0.29, p = 0.0098). The results further support the evidence that the repeat expansion at the chromosome 16q24.3 locus is the direct cause of HDL2 and provide preliminary guidelines for the genetic testing of patients with an HD‐like phenotype. Ann Neurol 2004 An Erratum has been published for this article in Ann Neurol 56: 911, 2004 .