遗传性脊髓小脑型共济失调7型临床特征及基因突变分析

Clinical Features and Mutation Analysis on Spinocerebellar Ataxia 7

目的分析中国汉族人群ATXN7基因突变,探讨遗传性脊髓小脑型共济失调7型(SCA7)患者临床特征。方法运用聚合酶链反应、变性聚丙烯酰胺凝胶电泳和毛细管电泳方法对521例临床诊断为SCA的患者(337例常染色体显性遗传先证者,184例散发患者)及258名健康对照人群进行ATXN7基因CAG三核苷酸重复突变分析,并对有ATXN7基因异常的7个家系进行临床总结。结果337例常染色体显性遗传先证者中发现7个ATXN7基因CAG三核苷酸异常重复扩增突变(2.08%),其异常重复次数范围为38～71次;184例散发患者未发现CAG三核苷酸异常重复扩增突变。258名健康对照者中共发现13种等位基因,CAG重复次数范围为5～17次,平均10.23次,以10次CAG三核苷酸重复最常见。7个SCA7家系临床主要表现为共济失调、视力下降、眼底病变,同时可合并其他多种少见临床症状,在父系遗传时存在明显的遗传早现现象。结论SCA7多呈常染色体显性遗传,散发病例罕见,临床表现复杂,进行ATXN7基因突变分析有助于临床诊断。

Objective To perform the mutation analysis of ATXN7 gene in Chinese Han nationality, and to investigate the clinical characteristics of spinocerebellar ataxia type 7（SCA7）. Methods CAG trinucleotide repeat number detection of ATXN7 gene, in 521 SCA probands （337 were autosomal dominant ataxia. 184 were sporadic） and 258 healthy individuals, were carried out by PCR and denaturing polyaerylamide gel or capillary electrophoresis, following with summarization of the clinical characteristics of the seven SCA7 pedigrees. Results Seven probands with A TXN7 mutation were segregated among 337 ADCA pedigrees （2.08 %）. There was no ATXN7 mutation found in the 184 SCA sporadic patients by PCR and DPAGE, and the extent of abnormal repeat number was 38 71（58.22 in average）. Thirteen alleles were found by CE method in the 258 controls, and the extent of normal repeat number was 5 to 17 （10.23 in average）, Ten repeats of CAG appeared most frequently.The main characters of seven SCA7 pedigrees contained cerebellar ataxia, decreased visional acuity, pigmentary retinopathy together with some unusual clinical symptoms. Obvious anticipation occurred in paternal transmission. Conclusions We found most patients with SCA7 were autosomal dominant inheritance. Sporadic cases were rare and with complicate clinical characters. Performation of mutation analysis of ATXN7 gene was useful for the clinical diagnosis.