Detecting novel gene mutations in Usher syndrome families by next generation sequencing technology
作者单位：Key Laboratory of birth defects prevention and control Department of Medical Genetics Liuzhou Municipal Maternity and Child Healthcare Hospital Center of Hearing Liuzhou Municipal Maternity and Child Healthcare Hospital
会议名称：《中华医学会第十五次全国医学遗传学学术会议暨中国医师协会医学遗传医师分会第一届全国学术会议暨2016年浙江省医学遗传学年会》
会议日期：2016年
学科分类：100208[医学-临床检验诊断学] 1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学]
摘 要：Objective Usher syndrome(USH) is an autosomal recessive disorder characterized by hearing impairment and vision dysfunction due to retinitis pigmentosa. Phenotypic and genetic heterogeneities of this disease make it impractical to obtain a genetic diagnosis by conventional Sanger sequencing. Method This study explored an approach for detecting disease-causing genetic mutations in candidate genes in 25 cases from unrelated USH families based on targeted next-generation sequencing(NGS) technology. Through systematic data analysis using an established bioinformatics pipeline, all variants that passed filter criteria were validated by Sanger sequencing and co-segregation analysis. Result 44 pathogenic mutations in the USH disease genes were identified in the 25 USH families. We identified 7 novel mutations in CDH23 gene, 9 novel mutations in GPR98 gene, 2 novel mutations in MYO7 A gene, one mutations in PCDH15 gene, one mutations in USH1 C gene, and 12 novel mutations in USH2 A gene. All novel variations segregated with the disease phenotypes in their respective families and were absent from ethnically matched control individuals. Conclusion Targeted exome sequencing precisely and rapidly identified the genetic defects in 25 Chinese USH families and this technique can be applied as a routine examination for these disorders with significant clinical and genetic heterogeneity.