遗传性脊髓小脑型共济失调7型一家系的临床及基因突变分析

Clinical and mutation analysis of hereditary spinocerebellar ataxia type 7 from a Chinese predigree

目的研究中国人遗传性脊髓小脑型共济失调7型(SCA7)的基因突变和临床特征。方法应用聚合酶链反应(PCR)、聚丙烯酰胺凝胶电泳(PAGE)等技术对一个表现为共济失调、视力下降、视网膜变性的家系(6位成员,包括2个患者)的SCA7基因内CAG三核苷酸重复序列进行检测,并对异常等位基因片段进行DNA直接测序,分析基因型和表型之间的关系。结果检测出该家系内2个患者的SCA7等位基因CAG重复数目为71,而该家系内其他表型正常的SCA7等位基因CAG重复数目为7～9。结论CAG过度扩增为SCA7的致病原因,分子遗传学分析有助于SCA7的诊断以及症状前患者的预测。

Objective To study the gene mutation and clinical characteristics of hereditary spinocerebellar ataxia type 7. Methods The region of the SCA7 gene containing the CAG repeat were amplified by means of polymerase chain reaction （ PCR ） and polyacrylamide gel electrophoresis （PAGE） technique in a predigree （6 members including 2 patients ） characterized by cerebellum ataxia and decreased visional acuity, pigmentary retinopathy. The abnormal allele fragments were sequenced by ABI377 DNA sequencing machine. The correlation between the clinical manifestation and CAG repeat size in the SCA7 gene product was analyzed. Results Two patients in this predigree carried a 71-repeat allele. The alleles with 7 to 9 repeats were seen in 3 healthy members. Conclusions The expanded triplet repeats in the SCA7 gene contribute to the pathologic phenotype. Molecular genetic analysis is useful for the diagnosis of SCA7, prediction of presymptomatic patients and genetic counseling.