一例Usher综合征Ⅱ型患儿USH2A基因的致病变异分析

Analysis of pathogenic variants of USH2A gene in a child with Usher syndrome typeⅡ

目的分析1例Usher综合征Ⅱ型患儿听力障碍相关基因的致病性变异,为其临床诊断提供分子遗传学依据。方法采集患儿和父母外周血进行听力障碍者相关基因检测,100名无听力障碍作为正常对照。结果患儿USH2A基因存在第41内含子c.8224-1G>C和第28外显子c.5678C>G(p.Ser1893X)复合杂合变异,患儿的母亲为c.8224-1G>C杂合变异携带者,父亲为c.5678C>G杂合变异携带者。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,USH2A基因c.8224-1G>C和c.5678C>G变异均判定为致病性变异(PVS1+PM2+PM3)。结论USH2A基因c.8224-1G>C和c.5678C>G复合杂合变异可能为该患儿的致病原因,新变异的检出扩展了USH2A基因变异谱。

Objective To detect pathogenic variant in a child featuring Usher syndrome typeⅡ.Methods Peripheral blood samples of the child and his parents were collected for the analysis of variants of hearing impairment-related genes.The findings were verified in 100 individuals with normal hearing.Results The child was found to harbor compound heterozygous variants of the USH2A gene,namely c.8224-1G>C in intron 41 and c.5678C>G(p.Ser1893X)in exon 28,which were inherited respectively from his mother and father.Based on the American College of Medical Genetics and Genomics standards and guidelines,both c.8224-1G>C and c.5678C>G(p.Ser1893X)variants of USH2A gene were predicted to be pathogenic(PVS1+PM2+PM3).Conclusion The compound heterozygous variants c.8224-1G>C and c.5678C>G of the USH2A gene probably underlay the disease in this child.Above finding has enriched the spectrum of USH2A gene variants.