SCA1, SCA2, MJD/SCA3 (CAG)n mutation detection and analysis in patients with hereditary spinocerebellar ataxia from Chinese families

OBJECTIVE: To assess the frequency of the SCA1, SCA2, MJD/SCA3 CAG trinucleotide repeat expansions ((CAG)n) among individuals diagnosed with hereditary spinocerebellar ataxia (SCA) from Chinese families. METHOD: The SCA1, SCA2, MJD/SCA3 (CAG)n mutation were detected with the polymerose chain reaction (PCR), denaturing polyacrylamide gel and silver staining technique in 79 patients with autosomal dominant SCA from 50 Chinese families. RESULTS: Among 50 kindreds, 2% (1/50) had the SCA1, (CAG)n, 6% (3/50) had the SCA2, (CAG)n, whereas 48% (24/50) were positive for the MJD/SCA3 (CAG)n. Thus, together SCA1, SCA2, and MJD/SCA3 represent 56% (28/50) of the autosomal dominant ataxias in our group. In two SCA1 patients the CAG repeat was expanded to 53-62 repeats, whereas in normal ivdividuals was 12-36 repeats. In seven SCA2 patients the CAG repeat was expanded to 43-47 repeats, whereas in normal ivdividuals was 22-30 repeats. In forty-two MJD/SCA3 patients the CAG repeat was expanded to 63-78 repeats, whereas in normal ivdividuals was 15-38 repeats. The SCA1, SCA2, MJD/SCA3 (CAG)n mutation were excluded in the other 28 SCA patients from 22 families. CONCLUSION: The frequency of MJD/SCA3 is substantially higher than that of SCA1 and SCA2 in the autosomal dominant SCA from Chinese families. Chinese patients with MJD/SCA3 are non-Portuguese patients with MJD/SCA3. Clinical expressions of the various SCAs overlap one another, making a diagnostic classification based on phenotype inaccurate in many instances. It is important for SCA clinical study to make a SCA gene diagnosis and genomic classification.