一个脊髓小脑共济失调家系的分子遗传学研究

Molecular genetics of a Chinese family with spinocerebellar ataxia

目的研究1个汉族脊髓小脑共济失调（SCAs）家系的基因分型。方法收集该SCAs家系中的6例患者和有血缘关系的40例无症状者共46人的外周血样品,结合先证者的临床体征及二代测序结果,采用多聚酶链式反应（PCR）对该家系致病基因ATXN2的CAG三核苷酸重复片段进行扩增,通过琼脂糖凝胶电泳和PCR产物测序的方法确定该家系所有成员的正常与异常扩增等位基因内三核苷酸重复次数。结果该家系的遗传性SCAs为常染色体显性遗传,4代46人中有6例SCA2患者,7例为致病等位基因携带者。患者ATXN2两个等位基因中的1条CAG三核苷酸重复次数在正常范围内,另1条CAG三核苷酸重复次数在异常范围。患者异常等位基因CAG三核苷酸重复次数范围为40~46次。结论该家系为CAG三核苷酸重复序列动态突变引起的常染色体显性遗传性脊髓小脑共济失调Ⅱ型,基因诊断还发现该家系中有7名致病等位基因携带者。

Objective To study the genotype of the members of a Chinese family with spinocerebellar ataxia （SCA）. Methods The peripheral blood samples of 6 patients and 40 asymptomatic people belonged to the family were collected. Referring to the clinical manifestations of the proband and second-generation sequencing results, the CAG trinucleotide repeats of the pathogenic gene ATXN2 were amplified by polymerase chain reaction （PCR）. The repeated times of the trinucleotide in normally and abnormally amplified alleles were defined by agarose gel electrophoresis and PCR products sequencing. Results Autosomal dominant heredity was the cause of the SCA in this family. Six out of 46 in the fourth-generation were SCA2 patients, 7 were the carriers of pathogenic allele. The repeated times of CAG trinucleotide were within the normal range in one of the two alleles of ATXN2, but they were in abnormal range in the another one. The repeated times of CAG trinucleotide were 40-46 in abnormal alleles of patients. Conclusion Autosomal dominant heredity SCA2 has been diagnosed in this family caused by the dynamic nutation of CAG trinucleotide repeats, and 7 pathogenic allele carriers in this family were confirmed by genetic diagnosis.