Meiotic instability of the CAG repeats in the SCA6/CACNA1A gene in two Japanese SCA6 families.
Intergenerational stability of the CAG repeat number has been considered to be a specific molecular feature of SCA6 compared with other CAG repeat diseases. Nevertheless, we showed meiotic instability of the CAG repeats in the SCA6/CACNL1A gene in two Japanese SCA6 families, including de novo expansion. In one family, the CAG20 allele expanded to the CAG26 one during paternal transmission, and in the other family, the CAG19 allele expanded to the CAG20 one during maternal transmission. Although it is controversial as to whether the CAG20 allele is pathological or not, this is the first case of haplotype analysis-proven de novo expansion in SCA6, confirming the derivation of an expanded allele from one normal allele. We should carefully follow up the individuals carrying the CAG20 allele in our family who show normal neurological and radiological findings at present.
Shimazaki
H
H
Department of Neurology, Jichi Medical School, 329-0498, Tochigi, Japan.
Takiyama
Y
Y
Sakoe
K
K
Amaike
M
M
Nagaki
H
H
Namekawa
M
M
Sasaki
H
H
Nakano
I
I
Nishizawa
M
M
D000328:Adult; D000368:Aged; D000483:Alleles; D002531:Cerebellum / Q000473:pathology* / Q000503:physiopathology; D004252:DNA Mutational Analysis; D005260:Female; D006239:Haplotypes; D006801:Humans; D007564:Japan; D008297:Male; D008540:Meiosis / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D020754:Spinocerebellar Ataxias / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D019680:Trinucleotide Repeat Expansion / Q000235:genetics*