CAJ | 학술논문

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.
목적 대일개상염색체현성유전감람교뇌소뇌위축(olivopontocerebellar atrophy,OPCA)가계진행림상진단,탐토기림상특점병명학기기인진단.방법 완성가계조사,대포괄선증자재내적가계성원진행신경과체검,행두부핵자공진(magnetic resonance imaging,MRI)등보조검사,병진행기인진단.결과 해가계정상염색체현성유전,기중량례성원유명현이상림상표현,가족사조사현시령유9례유상사림상표현적성원이거세,두부MRI시소뇌、뇌간이급교뇌위축명현.결합가족사、림상표현이급MRI검사결과,기진단부합감람교뇌소뇌위축.대소유가계성원진행치병기인분석발현,척수소뇌공제실조2형(spinocerebellar ataxia type 2,SCA2)、3형(SCA3)、7형(SCA7)、12형(SCA12)이급치상핵홍핵창백구구뇌하부핵위축(dentatorubral-pallidoluy-sian atrophy,DRPLA)치병기인검측균정상.10례건강대조SCA1목적편단CAG중복수위29～37,이2례환자이상등위기인CAG중복수분별위53화67,5례무증상가계성원중,1례CAG중복수위57,학진위증상전환자,령외4례CAG중복수재29～37지간,배제환병가능.결론 해가계위CAG동태돌변인기적감람교뇌소뇌위축,림상특정존재이질성,기인진단부합SCA1.
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 SCA1. The clinical features of SCA1 are heterogeneous, so genetic diagnosis is very important.