小脑脊髓性共济失调8型的临床特点及遗传分析  

Clinical characteristics and genetic analysis of cerebellar spinal ataxia type 8

作　　者：陶建霞 郭硕 周妍冰 王旻晋[1] 周易[1] Tao Jianxia;Guo Shuo;Zhou Yanbing;Wang Minjin;Zhou Yi(Department of Laboratory Medicine,West China Hospital,Sichuan University,Chengdu 610041,China)

机构地区：[1]四川大学华西医院实验医学科,成都610041

出　　处：《国际遗传学杂志》2021年第3期146-151,共6页International Journal of Genetics

摘　　要：目的脊髓小脑性共济失调8型(spinocerebellar ataxia 8,SCA8)是一种由致病基因ATXN8OS非编码区CTA/CTG异常重复扩展引起的缓慢进行性共济失调。近年来SCA8在中国SCA患者中占比有所增高。本研究关注ATXN8OS基因(CTA/CTG)n扩展突变在中国大陆SCA患者中的分布,详细报道所发现的SCA8患者的临床特征,并比较其与SCA中最常见的SCA3患者临床特征的差异。方法应用荧光PCR和毛细管凝胶电泳等方法对700例未知分型的SCA患者(已排除SCA1、SCA2、SCA3、SCA6、SCA7、SCA12、SCA17和齿状核红核苍白球路易体萎缩症)进行ATXN8OS基因三核苷酸重复次数分析,并收集患者临床资料。另收集57例已通过基因及临床确诊为SCA3患者的临床资料。结果700例SCA患者中,有3例患者发现ATXN8OS基因(CTA/CTG)n核苷酸扩展突变,其中有1例后期完成家系追踪,另外2例为散在病例,其中1例有表现多系统萎缩症(multiple system atrophy,MSA)临床特征。余697例SCA患者中ATXN8OS基因(CTA/CTG)n变异范围为4~69次,平均重复次数(21.17±7.49)次,18次重复最常见,纯合子144例,纯合率为20.7%。SCA8和SCA3在临床上没有明显的差异,均有锥体、锥体外系体征和小脑萎缩等。结论中国人群ATXN8OS基因(CTA/CTG)n拷贝数分布可能存在一个整体偏低的特点,SCA8在中国并不罕见,其致病基因ATXN8OS基因(CTA/CTG)n扩展突变不稳定,可能在遗传过程中发生拷贝数改变。SCA8的发病年龄较SCA3晚,但患者临床表现相似;MSA可能是SCA8的不典型症状之一。因此,对临床疑似SCA或MSA患者进行ATXN8OS基因三核苷酸重复次数分析对临床诊疗具有重要意义。Objective Spinocerebellar ataxia type 8(spinocerebellar ataxia 8,SCA8)is a slowly progressive ataxia caused by the abnormal repeated expansion of CTA/CTG in the non-coding region of the pathogenic gene ATXN8OS.Recently,the proportion of SCA8 in Chinese patients with SCA has increased.This study focused on the distribution of ATXN8OS gene(CTA/CTG)n expansion mutation in SCA patients in mainland of China,and detailed the clinical features of SCA8 patients and compared them with the most common clinical features of SCA3 patients in SCA.Methods Fluorescence PCR and capillary gel electrophoresis were used to analyze the trinucleotide repeats of ATXN8OS gene in 700 patients with unknown typing of SCA(excluding SCA1,SCA2,SCA3,SCA6,SCA7,SCA12,SCA17 and globus pallidus atrophy of dentate nucleus),and the clinical data of the patients were collected,which included 57 patients with SCA3.Results The(CTA/CTG)n nucleotide extension mutations of ATXN8OS gene was found in three patients with SCA,one of them completed the pedigree follow-up at the later stage,and the other two patients were sporadic cases[one of which had clinical features of multiple system atrophy MSA].Among the other 697 SCA patients,the variation range of ATXN8OS gene(CTA/CTG)n was 4~69,and the average number of repeats was 21.17±7.49,18 repeats were the most common,and 144 homozygotes were found.The homozygous rate was 20.7%.There was no significant difference between SCA8 and SCA3 in clinic,but both had pyramidal and extrapyramidal signs and cerebellar atrophy.Conclusion The distribution of(CTA/CTG)n copy number of ATXN8OS gene in the Chinese population is low as a whole.SCA8 is not rare in China.The extended mutation of(CTA/CTG)n in the ATXN8OS gene is unstable and may change in the process of inheritance.The age of onset of SCA8 is later than that of SCA3,but the clinical manifestations of patients are similar,and MSA may be one of the atypical symptoms of SCA8.Therefore,the analysis of trinucleotide repeats of the ATXN8OS gene in patients with suspected

关 键 词：脊髓小脑共济失调 SCA8 SCA3 鉴别诊断 

分 类 号：R744.8[医药卫生—神经病学与精神病学]