广西一脊髓小脑共济失调3型家系SCA3/MJD基因突变和多态性的分析

常染色体显性脊髓小脑型共济失调(Autosomal dominant spinocerebellar ataxias, ADCAs)是一种神经系统退行性疾病, 具有高度的遗传异质性, 其中脊髓小脑型共济失调3型(Spinocerebellar ataxias type 3, SCA3)是一种常见的类型。文章通过PCR扩增广西一个脊髓小脑共济失调家系SCA3/MJD基因片段, 用毛细管电泳和测序方法检测了SCA3/MJD基因的CAG重复序列大小、传递特点以及SCA3/MJD基因的变异。结果显示：家系的所有4名患者和3名无症状携带者(Asymptomatic carrier)的SCA3/MJD基因第10外显子中存在异常扩增的CAG重复序列, 重复次数为64~71次; CAG重复次数在具有cgg等位基因的正常个体间传递时保持不变, 提示cgg等位基因不是正常个体两代间CAG重复序列稳定性的影响因素。SCA3/MJD基因中另有两个单碱基点突变, 一个是内含子区的杂合性突变(IVS9-113 T>C), 另一个是外显子区域的错义突变(220 G>A, 220 Glu>Gly)。这两个点突变为首次报道, 但尚不能明确这两个新的点突变对SCA3表型的影响。

Analysis of SCA3/MJD3 gene mutation and genetic polymorphism in a Guangxi family with spinocerebellar ataxia 3

Autosomal dominant cerebellar ataxias (ADCAs) comprise a group of genetically heterogeneous neurodegenerative disorders among which spinocerebellar ataxia type 3 (SCA3) represents the most common form of SCAs worldwide. The fragments of SCA3/MJD gene,which is the member of family GXPL1,were amplified by polymerase chain reaction (PCR). The PCR products of SCA3/MJD gene were detected with capillary electrophoresis (CE) and sequencing to evaluate the size of CAG repeats, feature in the transmission and the mutation in the family with SCA3 in Guangxi province. The results showed that the exon 10 of the SCA3/MJD gene contains 64—71 CAG repeats in all of the affected individuals and three asymptomatic carriers of the family. The number of the CAG repeats during transmission in the normal individuals carrying CGG allele remains consistent, suggesting that CGG allele could have no effect on intergenerational stability of CAG repeats in normal individuals. In addition, two novel point mutations were identified: IVS9-113 T>C in the intronic region and a missense mutation 220 G>A(Glu>Gly) in the encoding region. These two novel point mutations have not been reported and the effect of the mutations on the phenotype of SCA3 is not clear.