一个甲基丙二酸血症家系致病基因的遗传学研究

Genetic study of pathogenic genes in a family with methylmalonic academia

目的对一个甲基丙二酸血症家系进行相关致病基因突变分析,从遗传学角度明确其可能的发病原因。方法采用二代测序(next generation sequencing,NGS)方法对该家系胎儿样本进行目标序列靶向捕获测序技术(targeting sequencing,TS)检测,检出可疑致病位点后再结合PCR和Sanger测序,在家系内进行遗传共分离验证以及反转录PCR验证。结果检测到先证者胎儿在MUT基因上携带母源性c.753+1delinsTGGTTATT变异和父源性c.911+1G>C变异,该家系符合常染色体隐性遗传的遗传规律,而MUT基因是甲基丙二酸血症的常见致病基因,两处变异可以导致MUT基因转录本的异常。结论MUT基因是该家系的可能致病基因,二代测序结合Sanger测序可以快速准确地对甲基丙二酸血症家系进行基因诊断,为该家系的遗传咨询和产前诊断提供可靠方法和依据。

Objective To analyze the mutation of related pathogenic genes in a family with methylmalonic acidemia,and explore the possible causes of the disease from the perspective of genetics.Methods Targeting sequencing(TS)was carried out in fetal samples of the family through the next generation sequencing(NGS)method,the suspected pathogenic sites were detected,and then PCR and Sanger sequencing were combined for co-genetic isolation and verification in the family.Results The proband fetus was found to be a carrier with maternal c.753+1delinsTGGTTATT mutation and parent c.911+1G>C mutation on MUT gene,while MUT gene is a common pathogenic gene of methylmalonic acidemia.These two mutations led to the abnormal transcriptions of MUT gene.Conclusion MUT gene is a possible pathogenic gene of this family.NGS combined with Sanger sequencing can rapidly and accurately diagnose the gene of methylmalonic acidemia and provide a basis for the genetic counseling and the prenatal diagnosis of this family.