脊髓小脑共济失调的分子遗传学研究进展  

Recent Progress in the Molecular Genetics of Spinocerebellar Ataxias(SCAs)

作　　者：李仲宜[1] 张咸宁[2] 

机构地区：[1]宁波大学医学院附属医院宁波市医疗中心李惠利医院,浙江宁波315041 [2]浙江大学医学院医学遗传学室,浙江杭州310031

出　　处：《宁波大学学报（理工版）》2006年第1期127-131,共5页Journal of Ningbo University：Natural Science and Engineering Edition

基　　金：浙江省医药卫生科研项目(2002A080)

摘　　要：脊髓小脑共济失调（SCAs）是一组具有多变的小脑、脊髓小脑束和脑干神经元变性的异质性神经病．按照目前的分子分类法，SCAs包括SCA1～SCA27等亚型．SCAs同样具有遗传异质性，加上各亚型的临床症状有较多的重叠，使得临床亚型的确诊较为复杂．SCA1、SCA2、SCA3、SCA6、SCA7、SCA17和DRPLA由三核苷酸重复（CAG）n引起，SCA8和SCA10则分别由（CTG）n和（AT—TCT）n重复造成，而易感基因的点突变可能是SCA14和SCA27的分子病因．由于核苷酸重复的不稳定性，SCAs的一个主要特点是存在遗传早现．SCAs患者包含多聚谷氨酰胺的神经元核内及细胞质包涵体的作用不详，但其细胞内的蛋白质聚集现象可能是SCAs不同于其他异质性疾病的常见病理过程．Spinocerebellar ataxias（SCAs） are a heterogeneous group of neurological disorders characterized by variable degrees of degeneration of the cerebellum, spinocerebellar tracts, and brain stem neurons. The current molecular classification is based on the order of gene description（ SCA1 - SCA27）. SCAs are also genetically heterogeneous and the clinical diagnosis of subtypes of SCAs is complicated by the salient overlap of the phenotypes between genetic subtypes. Several identified mutations correspond to expansions of repeated trinucleotides （ CAG repeats in SCA1, SCA2, SCA3, SCA6, SCA7, SCA17 and DRPLA, CTG repeats in SCAB）. A pentanucleotide repeated expansion （ATFCT） is associated with SCA10. Missense mutations have also been found in SCA14 and SCA27. One main feature of SCAs is the existence of inheritance premature presence due to instability of expanded alleles. The role of polyglutamine-containing intranuclear and cytoplasmic inclusion bodies in SCA remains unknown, but protein aggregation may be the common step in the pathogenesis of these otherwise rather heterogeneous disorders.

关 键 词：脊髓小脑共济失调 动态突变 遗传早现 多聚谷氨酰胺病 

分 类 号：R744.7[医药卫生—神经病学与精神病学] R596[医药卫生—临床医学]