一个EYA1基因无义变异所致鳃-耳综合征家系的遗传学分析

Genetic analysis of a Chinese pedigree affected with branchiootic syndrome due to a nonsense variant of EYA1 gene

目的探讨1个疑似鳃-耳综合征家系的临床表型,寻找该家系的可能致病原因,为其临床诊断提供依据。方法应用目标序列捕获技术对先证者进行耳聋基因的筛查,找到可疑致病变异,并用Sanger测序对家系成员进行验证。结果遗传性耳聋基因筛查检测到先证者EYA1 c.1627C>T(p.Gln543Ter)无义变异;Sanger测序证实该家系中4例有鳃-耳综合征临床表型的患者均系EYA1 c.1627C>T(p.Gln543Ter)变异杂合子。根据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,EYA1 c.1627C>T(p.Gln543Ter)变异判定为致病性变异(PVS1+PS+PP3+PP4)。结论EYA1基因c.1627C>T(p.Gln543Ter)变异可能为该家系患者的致病原因,基因检测结果可以为其临床诊断提供依据。

Objective To analyze the clinical phenotype and genetic basis for a Chinese pedigree suspected for branchiootic syndrome(BOS).Methods The proband was subjected to target-capture high-throughput sequencing to detect potential variant of deafness-associated genes.Candidate variants were verified by Sanger sequencing of the family members.Results The proband was found to harbor a c.1627C>T(p.Gln543Ter)nonsense variant of the EYA1 gene.Sanger sequencing confirmed that all of the 4 patients with the BOS phenotype from the pedigree have harbored the same heterozygous variant.Based on the guidelines of the American College of Medical Genetics and Genomics,the variant was predicted to be pathogenic(PVS1+PS+PP3+PP4).Conclusion The c.1627C>T(p.Gln543Ter)variant of the EYA1 gene probably underlay the BOS phenotype in this pedigree.Above finding has provided a basis for its clinical diagnosis.