一个遗传性共济失调3型家系中致病ATXN3中间类型等位基因分析

目的 研究遗传性共济失调3型中间类型等位基因致病表型的临床表现与基因突变特点.方法 应用PCR、毛细微管电泳、分子克隆及测序等方法 对1个临床诊断为遗传性共济失调家系进行ATXN3基因检测,对异常片段进行分子克隆测序.结果 证实该家系为遗传性共济失调3型家系,先证者异常片段CAG重复次数为43次;患者两个儿子异常片段重复分别为41、64次.结论 中间类型等位基因在两代间遗传是不稳定的,重复次数的改变是双向的,43次CAG重复是目前报道的遗传性共济失调3型发病患者最小不稳定重复次数.本家系的研究结果 进一步缩短了正常CAG重复次数与异常重复次数之间的差距.

Identification of ATXN3 intermedial allele associated with a disease phenotype in an SCA3 Han Chinese family

Objective To investigate the clinical manifestation and the mutation characteristics of intermedial allele associated with a disease phenotype of a Machado-Joseph disease (MJD) family. Methods Polymerase chain reaction, capillary elcctrophorcsis, molecular cloning and sequencing were performed to detect the ATXN3 gene in an spinocerebellar ataxia(SCA) family. The fragments of expanded alleles were subcloned into the pGEM-T plasmids and sequenced. Results The expanded repeats at the MJD locus were confirmed by molecular technique. The proband had 43 CAG repeats at the MJD locus. He had two sons with 41 and 64 repeats in the expanded allele respectively. Conclusion A 43 CAG repeat allele was unstable upon inter-generational transmission. The change of the CAG repeat 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 the normal and expanded allele repeats.