非CAG三核苷酸异常扩增相关脊髓小脑共济失调患者CACNA1A基因突变分析张 槊,杨志华,刘玉涛,骆海洋
Analysis of CACNA1A gene mutation in patients with non-CAG repeat expansion-related spinocerebellar ataxia

目的:探讨中国人非CAG三核苷酸异常扩增相关脊髓小脑共济失调(SCA)患者CACNA1A基因的突变特点。方法:应用PCR联合DNA序列分析方法,对来自全国的68例排除CAG三核苷酸异常扩增基因的SCA家系的先证者进行CACNA1A基因突变分析。结果:68例先证者中发现1例CACNA1A缺失型变异,CACNA1A基因第19号外显子2 992位到2 997位碱基发生GAGGGC缺失变异,导致其所编码蛋白Cav2.1第998位谷氨酸和999位甘氨酸缺失。结论:在中国人非CAG三核苷酸异常扩增相关SCA家系中发现了CNCNA1A基因的缺失突变,表明CACNA1A基因突变可能是SCA的致病原因之一。
Aim: To investigate the mutation characteristics of CACNA1A gene in Chinese patients with non-cytosine-adenine-guanine(CAG)repeat expansions spinocerebellar ataxia(SCA)and provide new targets of gene diagnosis of SCA.Methods: Mutation analysis of CACNA1A gene was performed by use of PCR combined with DNA direct sequencing in 68 unrelated non-CAG repeat expansion-related SCA probands in China.Results: A deletion mutation was found in a patient, and molecular genetic analysis revealed that the patient had a mutation of c.2 992-2 997del in exon 19 of CACNA1A gene, which resulted in the amino acid deletion of p.Glu998-Gly999del.Conclusion: There is a mutation of CACNA1A gene in the family with SCA excluded genes with CAG repeat expansion, which demonstrates that mutation of CACNA1A gene may be a causative factor in Chinese SCA patients