2个Huntington病家系临床特征及CAG重复性分析

Clinical characteristics of Huntington disease in two pedigrees and analysis of expanded CAG trinucleotide repeat

目的：探讨Huntington病（Huntington disease,HD）的临床和遗传特征。方法：对收集的2个中国汉族HD家系患者的临床资料进行综合分析,应用聚合酶链式反应及基因扫描方法对其中9例家系成员的IT15基因的三核苷酸重复序列进行分析。结果：在两个家系中确诊了6例患者（男女均有发病）,患者IT15基因的基因型均为杂合子,致病CAG重复拷贝数介于4078次。两个家系中子代较父代发病年龄提前,家系2中可见发病年龄与CAG重复拷贝数呈负相关。6例患者中有1例为少年型HD,其临床表现明显不同于成人型,以肌张力障碍为主要表现。结论：HD是一种由CAG重复序列异常扩增所致的神经变性病,存在遗传早现现象;少年型HD的临床表现不同于成人型,CAG重复拷贝数与发病年龄及疾病严重程度有关。

Objective： To understand the clinical and genetic features of Huntington disease（HD）.Methods： The clinical data of HD cases from 2 Chinese families were analyzed and trinucleotide repeat in the IT15 gene were investigated in 9 of the two families by polymerase chain reaction and GeneScan.Results： Among the two pedigrees,6 cases were ascertained as HD by genetic test.Genotypes of IT15 were heterozygous in these HD patients.CAG repeat of the patients in the HD chromosome were 40-78.In the two pedigrees,the onset age was earlier in the subsequent generations than that of their fathers.In pedigree 2,the onset age was inversely correlated with CAG repeat number.One out of the 6 cases was juvenile-onset type of Huntington disease,whose clinical symptoms were different from those of the adult-onset cases,especially the hypertonic manifestation.Conclusion： HD is an autosomal dominant neurodegenerative disorder with genetic anticipation caused by enlargement of CAG repeat in IT15 gene.The clinical manifestation is different between the juvenile-onset and the adult-onset.The number of CAG repeat is inversely correlated with the onset age and clinical severity.