Sisters homozygous for the spinocerebellar ataxia type 6 (SCA6)/CACNA1A gene associated with different clinical phenotypes.
Spinocerebellar ataxia type 6 (SCA6) is a neurodegenerative disease caused by a CAG repeat expansion in the CACNA1A gene. The neurodegeneration that occurs in CAG repeat diseases is considered to share a common mechanism that may result in the gain of a toxic function related to the expanded polyglutamine tracts. However, the phenotypic expression in homozygotes for CAG repeat diseases has been controversial, and is not clearly related to a gain of functional mechanism. We identified a Japanese family with two sisters who were homozygous for the SCA6 with identical CAG repeat expansion (25/25). They showed an earlier age of onset (27 years in both) than their father (44 years), a heterozygote with an expanded allele showing the same CAG repeat length as the homozygotes (25/14). Interestingly, the two sisters showed differences in disease progression and severity, although the age of onset and CAG repeat length were identical. These findings strongly suggest that the gene dosage influences the age of onset, but other unknown factors are also important in the phenotypic expression of homozygous SCA6.
Kato
T
T
Department of Neurology, Kasugai Municipal Hospital, Japan.
Tanaka
F
F
Yamamoto
M
M
Yosida
E
E
Indo
T
T
Watanabe
H
H
Yoshiwara
T
T
Doyu
M
M
Sobue
G
G
D000328:Adult; D017668:Age of Onset; D000368:Aged; D015220:Calcium Channels / Q000235:genetics*; D004247:DNA / Q000032:analysis; D005260:Female; D006720:Homozygote; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009679:Nuclear Family; D010375:Pedigree; D016133:Polymerase Chain Reaction; D020754:Spinocerebellar Ataxias / Q000235:genetics*; D019680:Trinucleotide Repeat Expansion; D020864:Calcium Channels, N-Type
D015220:Calcium Channels; D004247:DNA; C105656:CACNA1A protein, human; D020864:Calcium Channels, N-Type