Huntington's Disease-like 2 (HDL2) in North America and Japan.
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 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.
Margolis
Russell L
RL
Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. rmargoli@jhmi.edu
Holmes
Susan E
SE
Rosenblatt
Adam
A
Gourley
Lisa
L
O'Hearn
Elizabeth
E
Ross
Christopher A
CA
Seltzer
William K
WK
Walker
Ruth H
RH
Ashizawa
Tetsuo
T
Rasmussen
Astrid
A
Hayden
Michael
M
Almqvist
Elisabeth W
EW
Harris
Juliette
J
Fahn
Stanley
S
MacDonald
Marcy E
ME
Mysore
Jayalakshmi
J
Shimohata
Takayoshi
T
Tsuji
Shoji
S
Potter
Nicholas
N
Nakaso
Kazuhiro
K
Adachi
Yoshiki
Y
Nakashima
Kenji
K
Bird
Thomas
T
Krause
Amanda
A
Greenstein
Penny
P
D000328:Adult; D017668:Age of Onset; D005260:Female; D005838:Genotype; D006801:Humans; D006816:Huntington Disease / Q000453:epidemiology / Q000235:genetics*; D007564:Japan / Q000453:epidemiology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D009656:North America / Q000453:epidemiology; D010375:Pedigree; D012091:Repetitive Sequences, Nucleic Acid; D019680:Trinucleotide Repeat Expansion / Q000235:genetics*
D008565:Membrane Proteins; C412507:junctophilin