A Japanese family with spinocerebellar ataxia type 6 which includes three individuals homozygous for an expanded CAG repeat in the SCA6/CACNL1A4 gene

• Published in: Journal of the neurological sciences Vol. 158; no. 2; pp. 141 - 147
• Main Authors: Takiyama, Yoshihisa, Sakoe, Kumi, Namekawa, Michito, Soutome, Michiyo, Esumi, Eisaku, Ogawa, Tomoko, Ishikawa, Kin-ya, Mizusawa, Hidehiro, Nakano, Imaharu, Nishizawa, Masatoyo
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier B.V 30.06.1998; Elsevier Science
• Subjects: Aged; Aged, 80 and over; Anticipation; Base Sequence; Biological and medical sciences; Brain - pathology; CAG repeats; Calcium Channels - genetics; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Down-beat nystagmus; Female; Homozygote; Humans; Japan; Magnetic Resonance Imaging; Male; Medical sciences; Middle Aged; Neurology; Pedigree; Repetitive Sequences, Nucleic Acid; Spinocerebellar Degenerations - classification; Spinocerebellar Degenerations - diagnosis; Spinocerebellar Degenerations - genetics; The SCA6/CACNL1A4 gene; Japan; Homozygote; Down-beat nystagmus; Anticipation; CAG repeats; The SCA6/CACNL1A4 gene; Human; Nervous system diseases; Family study; Clinical form; Genotype; Ionic channel; Homozygosity; Subunit; Genetic determinism; Cerebral disorder; Genetic disease; Phenotype; Calcium ion; Gene; Spinocerebellar ataxia; Central nervous system disease; Degenerative disease; Spinal cord disease
• ISSN: 0022-510X; 1878-5883
• DOI: 10.1016/S0022-510X(98)00108-7

We describe a Japanese family which includes 13 patients in five generations who have dominantly inherited ataxia. Molecular testing revealed that in these patients the SCA6/CACNL1A4 gene carries the smallest known expanded CAG repeat (21 repeat units). The clinical features of these patients exhibited predominantly cerebellar ataxia with onset late in adult life and a very slowly progressive disease course. In addition, this SCA6 family showed some characteristic clinical and genetic features, including (1) apparent lack of genetic anticipation, with an intergenerationally stable CAG repeat size and (2) down-beat nystagmus and diabetes mellitus in some of the SCA6 patients. We identified three individuals homozygous for an expanded CAG repeat (21/21) in the SCA6/CACNL1A4 gene, two of whom were symptomatic. There were no apparent differences in clinical phenotype between the individuals homozygous and those heterozygous for an expanded CAG repeat in the SCA6/CACNL1A4 gene.