橄榄桥脑小脑萎缩一家系的临床和遗传学研究  

The clinical features and genetic diagnosis in a large olivopontocerebellar atrophy type 1 family

作　　者：郭洪[1] 史树贵[2] 白云[1] 陈康宁[2] 傅勇[1] 胡华梅[1] 王凯[1] 

机构地区：[1]第三军医大学基础部医学遗传学教研,重庆400038 [2]第三军医大学西南医院神经内科,重庆400038

出　　处：《国际遗传学杂志》2010年第5期310-313,共4页International Journal of Genetics

基　　金：重庆市自然科学基金（2009BA5013）

摘　　要：目的 对一个常染色体显性遗传橄榄桥脑小脑萎缩（olivopontocerebellar atrophy,OPCA）家系进行临床诊断,探讨其临床特点并明确其基因诊断.方法 完成家系调查,对包括先证者在内的家系成员进行神经科体检,行头部核磁共振（magnetic resonance imaging,MRI）等辅助检查,并进行基因诊断.结果 该家系呈常染色体显性遗传,其中两例成员有明显异常临床表现,家族史调查显示另有9例有相似临床表现的成员已去世,头部MRI示小脑、脑干以及桥脑萎缩明显.结合家族史、临床表现以及MRI检查结果,其诊断符合橄榄桥脑小脑萎缩.对所有家系成员进行致病基因分析发现,脊髓小脑共济失调2型（spinocerebellar ataxia type 2,SCA2）、3型（SCA3）、7型（SCA7）、12型（SCA12）以及齿状核红核苍白球丘脑下部核萎缩（dentatorubral-pallidoluy-sian atrophy,DRPLA）致病基因检测均正常.10例健康对照SCA1目的片段CAG重复数为29～37,而2例患者异常等位基因CAG重复数分别为53和67,5例无症状家系成员中,1例CAG重复数为57,确诊为症状前患者,另外4例CAG重复数在29～37之间,排除患病可能.结论 该家系为CAG动态突变引起的橄榄桥脑小脑萎缩,临床特征存在异质性,基因诊断符合SCA1.Objective To make clinical and genetic diagnosis of members within a family with an autosomal dominant olivopontocerebellar atrophy, and to analyze the relationship between clinical features and genotype. Methods Pedigree analysis, the neurological examination, accessory test like brain MRI, and the molecular genetic analysis of the coding region of SCA1（spinocerebellar ataxia type 1）、SCA3 、SCA7 、SCA12 and DRPLA（dentatorubral and palliodoluysian atrophy）. Results The family manifested an autosomal dominant inheritance. In the two typical patients, brain MRI showed remarkable atrophy on cerebellum、brain stem and pons varolii. The CAG lengths of SCA3 、SCA7、SCA12 and DRPLA were normal in all family members. CAG repeat sizes of SCA1 ranged from 29 to 37 repeats in 10 healthy controls and 4 unaffected family members, whereas in the two patients, Ⅳ3 and Ⅳ7, the mutated allele were 53 and 67 respectively. The daughter of Ⅳ3 was diagnosed as presymptomatic SCA1 patient, due to the fact that she carries the mutated allele 57.Conclusion This family was genetically and clinically diagnosed to be autosomal dominant SCAI. The clinical features of SCA1 are heterogeneous, so genetic diagnosis is very important.

关 键 词：脊髓小脑共济失调 橄榄桥脑小脑萎缩 动态突变 家系 基因诊断 

分 类 号：R742[医药卫生—神经病学与精神病学]