COL4A5基因新变异导致遗传性血尿肾病耳聋综合征一家系

Identification of a novel variant of COL4A5 gene in a pedigree affected with Alport syndrome

目的:探讨1个遗传性血尿肾病耳聋综合征(Alport综合征)家系的致病原因。方法:应用高通量测序和Sanger测序法检测先证者COL4A5基因的变异,并在家系其他成员及100名正常对照中进行Sanger测序验证。结果:测序结果显示该家系中的4例女性患者COL4A5基因均存在c.3293G>T(p.Gly1098Val)的杂合变异,2例男性患者为COL4A5基因c.3293G>T(p.Gly1098Val)变异半合子,而正常家系成员以及100名正常对照中均未检测到此变异。按照美国医学遗传学与基因组学学会遗传变异分类标准与指南,COL4A5基因c.3293G>T变异位点判读为致病性变异(PM1+PM2+PP1-S+PP3+PP4)。结论:COL4A5基因的c.3293G>T(p.Gly1098Val)变异会导致Gly-X-Y三联结构发生变化,可能是该家系的发病原因,新变异的检出丰富了COL4A5基因的变异谱。

Objective To explore the genetic basis for a pedigree affected with Alport syndrome.Methods Next generation sequencing and Sanger sequencing was carried out to detect potential variant of the COL4A5 gene among members from the pedigree and 100 unrelated healthy controls.Results A novel missense c.3293G>T(p.Gly1098Val)variant was found in the COL4A5 gene among 6 affected members but not the unaffected members of the pedigree or the 100 healthy controls.According to the American College of Medical Genetics and Genomics standards and guidelines,the c.3293G>T variant was classified as pathogenic(PP1-strong+PM1+PM2+PP3+PP4).Conclusion By destructing the Gly-X-Y structure of its protein product,the c.3293G>T variant of the COL4A5 gene probably underlies the Alport syndrome in this pedigree.Above finding has enriched the spectrum of COL4A5 variants.