马查多-约瑟夫病/脊髓小脑型共济失调Ⅲ型患者(CAG)n拷贝数与临床特征

CAG repeat length and clinical features in Machado Joseph disease and type 3 spinocerebellar ataxia.

目的探讨马查多约瑟夫病基因１（ＭＪＤ１）ＣＡＧ三核苷酸动态突变及其拷贝数与ＭＪＤ／脊髓小脑型共济失调Ⅲ型（ＳＣＡ３）患者临床特征的相关关系。方法应用聚合酶链式反应、变性聚丙烯酰胺凝胶电泳和银染技术，对９个ＭＪＤ／ＳＣＡ３家系１０９名成员进行ＭＪＤ１基因（ＣＡＧ）ｎ拷贝数分析。结果发现异常扩增的（ＣＡＧ）ｎ拷贝数与发病年龄呈负相关，并在一定程度上影响病情严重程度；主要临床症状、体征与异常扩增的（ＣＡＧ）ｎ拷贝数无关，而是受病程影响。同时发现１７例症状前患者。结论异常扩增的（ＣＡＧ）ｎ拷贝数对疾病表型有影响。

s Objective To assess MJD1 gene (CAG)n dynamic mutation and the correlation between MJD1 gene (CAG)n copies and clinical features of MJD/SCA3 patients.Methods The polymorphic CAG repeat in the MJD1 gene was determined with polymerase chain reaction and denaturing polyacrylamide gel electrophoresis analysis in 109 members of 9 unrelated MJD/SCA3 families.Results The size of expanded CAG repeat was inversely correlated with the age of onset of MJD/SCA3, which also affected the severity of disease to a certain extent. It displayed inter generational instability. But instability of the expanded triplet repeat was not found to be affected by sex of the parent transmitting the mutaion. In addition, major clinical symptoms and signs were not correlated with CAG repeat lengths. Seventeen asymptomatic carriers were founol in the study.Conclusions Although (CAG)n copies influence on disease phenotype, it couldnt be made as the only predictable index of clincal features were found in the study.