3例家族性Alport综合征遗传咨询和产前诊断的临床病例分析

Clinical analysis of 3 cases of familial Alport syndrome with genetic counseling and prenatal diagnosis

目的:利用高通量测序(NGS)技术分析家族性Alport综合征(AS)的致病性突变及遗传方式,为咨询者提供准确的遗传咨询并给予产前诊断。方法:对3例家族性AS先证者进行致病性突变分析及家系验证,对遗传咨询者进行产前诊断。结果:3例先证者均发现AS致病基因COL4A5点突变,突变位点分别位于c2633G→A、c1769A→C、c1352G→A,经家系验证均为致病性突变。对3例咨询者胎儿DNA进行Sanger验证(第一代DNA测序技术),提示1例胎儿携带AS致病基因COL4A5的错义突变,2例未检测出致病性突变。结论:认识AS遗传方式的多样性和遗传特征,强调重视先证者的基因诊断及家系验证,确定遗传方式,建议行遗传咨询并给予生育指导。

Objective:To analyze the pathogenic mutation and genetic characteristics of familial Alport syndrome(AS),to make prenatal diagnosis to the consultants by the NGS method(Next Generation sequencing technology).Methods:Pathogenic mutation analysis and pedigree validation were carried out in 3 cases of familial AS probands,and prenatal diagnosis was made for genetic counselors.Results:The three probands all found mutations in the pathogenic gene COL4 A5.The mutations were located in c2633 G A,c1769 A C,c1352 G A,respectively.All the mutations were pathogenic by family verification.Sanger validation(first generation DNA sequencing) was performed on amniotic fluid of 3 consultants.The results showed that 1 fetus of three cases carried a missense mutation of AS pathogenic gene COL4 A5,and 2 cases did not detect the mutation.Conclusion:We should understand the diversity and genetic characteristics of AS genetic mode,make genetic testing and family validation of the proband before pregnancy to determine the genetic mode,and then give birth guidance after genetic counseling.