Analysis On The Gene Mutation Of SCA3 And SCA7 In Two SCAs Families

Objective : To investigate the clinical manifestation and the gene mutation characteristics of two SCAs families from Xinjiang. Methods:We examined three patients and nine families'members of two SCAs families from Xinjiang. Polymerase chain reaction, capillary electrophoreses technique, molecular cloning and sequencing were performed to detect SCA3 and SCA7 gene in two SCA families. The expanded alleles fragments were subcloned into the pGEM-T plasmids and sequenced, and sequencing was used to detect SCA7 gene in 40 Hui Chinese controls. Results:An SCA3 Han Chinese family and an SCA7 Hui Chinese family were confirmed by molecular technique. For the SCA3 family,the proband had 43 CAG repeats at MJD locus. He had two sons with 41 and 64 repeats in the expanded allele respectively. For the SCA7 family,molecular analysis demonstrated pathological expansions in the SCA7 gene ,with detection of 46 repeats in the expanded allele of the proband's father. The 46 repeats got expansion to 54 repeats in paternal transmission with marked anticipation of approximately 22 years. Three alleles were found by sequencing in the 40 Hui Chinese health persons. The most common allele was 10 repeats and the frequency was 90 % in the controls. Conclusion:1. A 43 repeats allele at MJD locus was unstable upon inter-generational transmission. The change of the CAG repeats was bidirectional. This is the shortest expanded allele associated with a disease phenotype in the MJD gene reported to date. The identification of the MJD family has reduced the amplitude between normal and expanded allele repeats. 2. The SCA7 family was the first SCA7 Hui Chinese family reported. Retinal degeneration is relatively unique to SCA7. The instability of the expanded triplet repeats accounts for the marked anticipation and the rate of progression of the disease.