ABSTRACT
Objective To study the gene mutation and clinical characteristics of hereditary spinocerebellar ataxia type 6 (SCA6) from two Chinese families Methods The SCA6 (CAG)n trinucleotide repeat mutations were detected using polymerase chain reaction (PCR) and polyacrylamide gel electrophoresis (PAGE) technique in 210 patients with autosomal dominant SCA from 120 families and 47 sporadic SCA patients,and 50 healthy persons were used as controls. The abnormal allele fragments were sequenced by ABI 377 DNA sequencing machine Results Two SCA families (four patients) had abnormal SCA6 alleles with the CAG repeat expanded to 25 and 26 repeats respectively, as confirmed by DNA sequencing, of which 1.7% (2/120 ) was about the positive rate. Normal SCA6 alleles were carried from 5 to 16 CAG repeats, whereas pathological alleles carry 7 to 17. Analysis of parent child couples demonstrated the existence of marked anticipation with earlier age of onset and a more rapid clinical course in successive generations. The intergenerational stability was noted in the number of CAG repeat. Conclusions Two SCA6 pedigrees have been firstly determined in Chinese from the clinical and genomic aspects. CAG expansions were suggested as the pathogenic cause of SCA6.