脊髓小脑性共济失调12型的分子遗传学诊断及临床分析

[目的]研究分析脊髓小脑性共济失调12型(SCA12)的分子诊断及临床表现特征.[方法]对临床诊断为脊髓小脑性共济失调(SCA)的36个家系43例患者、38例散发患者、60名家系"健康"个体及44名正常对照,通过聚合酶链反应(PCR)对SCA12基因含有CAG三核苷酸重复片段进行扩增,并利用ABI 373测序仪对异常等位基因片段进行DNA测序,聚丙烯酰胺凝胶电泳并以图像分析软件计算其长度,推算所有正常和异常扩增等位基因内CAG重复次数.[结果]正常我国南方汉族人群SCA12等位基因CAG重复数目为22～27.检出1个家系患者1例,症状前患者2例,两个等位基因中一个异常等位基因内CAG重复数目为68次.[结论]SCA12比较罕见,CAG三核苷酸重复异常扩增是其致病原因,分子遗传学分析可确证临床诊断和症状前诊断,并可为遗传咨询提供依据.该例为国内首次报道.

Molecular Genetic Diagnosis and Clinical Analysis on Spinocerebellar Ataxia Type 12

To study the molecular genetic diagnosis and clinical characteristics of spinocerebellar ataxia type 12 (SCA12). 43 patients with autosomal dominant SCA from 36 families, 38 sporadic SCA patients, 60 healthy individuals from the SCA families and 44 normal controls were studied. CAG dynamic mutation in SCA12 gene were detected by polymerase chain reaction(PCR), denaturing polyacrylamide gel electrophoresis and silver staining technique. The abnormal allele fragments were sequenced by ABI 373 DNA sequencing machine and the repeat number was caculated.One symptomatic and two presymptomatic SCA patients were found. The CAG repeat of one abnormal SCA12 allele expanded to 68 repeats. Normal alleles of SCA12 in Hans of South China had CAG repeats ranging from 22 to 27.[Conclusion]SCA12 is rare. CAG expansions are its pathogenic cause. Molecular genetic detection is an effective way for confirmation of clinic diagnosis and presymptomatic diagnosis and helpful to genetic counseling. This case is the first report in China.