TY - JOUR
T1 - Huntington's disease-like 2 (HDL2) in North America and Japan
AU - Margolis, Russell L.
AU - Holmes, Susan E.
AU - Rosenblatt, Adam
AU - Gourley, Lisa
AU - O'Hearn, Elizabeth
AU - Ross, Christopher A.
AU - Seltzer, William K.
AU - Walker, Ruth H.
AU - Ashizawa, Tetsuo
AU - Rasmussen, Astrid
AU - Hayden, Michael
AU - Almqvist, Elisabeth W.
AU - Harris, Juliette
AU - Fahn, Stanley
AU - MacDonald, Marcy E.
AU - Mysore, Jayalakshmi
AU - Shimohata, Takayoshi
AU - Tsuji, Shoji
AU - Potter, Nicholas
AU - Nakaso, Kazuhiro
AU - Adachi, Yoshiki
AU - Nakashima, Kenji
AU - Bird, Thomas
AU - Krause, Amanda
AU - Greenstein, Penny
PY - 2004/11
Y1 - 2004/11
N2 - 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 (r2 = 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.
AB - 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 (r2 = 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.
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U2 - 10.1002/ana.20248
DO - 10.1002/ana.20248
M3 - Article
C2 - 15468075
AN - SCOPUS:9144245757
SN - 0364-5134
VL - 56
SP - 670
EP - 674
JO - Annals of neurology
JF - Annals of neurology
IS - 5
ER -