Zhang Chuan, Hao Shengju, Liu Yali, Zhou Bingbo, Liu Furong, Zheng Lei, Ma Panpan, Liu Qing, Lin Xiaojuan, Yan Yousheng, Zhang Qinghua
Gansu Provincial Maternal and Child Health Care Hospital, Gansu Provincial Key Laboratory of Birth Defects Prevention and Control, Lanzhou, Gansu, China.
National Research Institute for Family Planning, Beijing, China.
J Int Med Res. 2019 Dec;47(12):6082-6090. doi: 10.1177/0300060519884197. Epub 2019 Nov 10.
To perform molecular diagnosis and genetic counseling in a young Chinese couple with congenital hearing loss.
Variant screening analysis was performed by PCR and direct Sanger sequencing or targeted next-generation sequencing of all known hearing loss genes. Novel variants were evaluated by PolyPhen2 and PROVEAN software tools to evaluate possible effects on protein function.
We identified causative variants in the young couple: c.235delC (rs80338943)/c.299-300delAT (rs111033204) compound heterozygous variants of in the husband and c.1828G>A (p.Glu610Lys, rs535637788)/c.2825-2827delAGA compound heterozygous variants of in the wife. The c.1828G>A variant has only previously been reported in a Mexican-American individual in the 1000 Genomes Project database. Using PolyPhen2 and PROVEAN, we speculated that the variant c.1828G>A is potentially pathogenic.
We carried out molecular diagnosis in a young couple with congenital hearing loss, and identified different disease-causing genes in the two individuals. The variant c.1828G>A present in the wife had not previously been reported in individuals with congenital hearing loss. We determined this to be a potential pathogenic variant, and a novel variant associated with hearing loss in a Chinese individual.
对一对患有先天性听力损失的年轻中国夫妇进行分子诊断和遗传咨询。
采用聚合酶链反应（PCR）和直接桑格测序法或对所有已知听力损失基因进行靶向二代测序，进行变异筛查分析。通过PolyPhen2和PROVEAN软件工具评估新变异对蛋白质功能的可能影响。
我们在这对年轻夫妇中鉴定出致病变异：丈夫为c.235delC（rs80338943）/c.299 - 300delAT（rs111033204）复合杂合变异，妻子为c.1828G>A（p.Glu610Lys，rs535637788）/c.2825 - 2827delAGA复合杂合变异。c.1828G>A变异此前仅在千人基因组计划数据库中的一名墨西哥裔美国人中报道过。使用PolyPhen2和PROVEAN，我们推测c.1828G>A变异具有潜在致病性。
我们对一对患有先天性听力损失的年轻夫妇进行了分子诊断，在两人中鉴定出不同的致病基因。妻子中存在的c.1828G>A变异此前在先天性听力损失个体中未见报道。我们确定其为潜在致病变异，是与一名中国个体听力损失相关的新变异。
