中华耳科学杂志2023，Vol.21Issue(6)：876-881,6.DOI:10.3969/j.issn.1672-2922.2023.06.020
USH2A基因大片段重复等突变导致中重度听力损失
Large Fragment Duplication and Other Mutations in USH2A Lead to Moderate to Severe Hearing Loss
摘要
Abstract
Objective To identify causative mutations in autosomal recessive hearing loss in two small families and provide genetic guidance for their reproductive planning.Methods High-throughput sequencing was used to screen 406 targeted deafness genes for candidate pathogenic mutations.Pedigree investigation,clinical examination and analy-sis of genetic characteristics were completed in the two families(J193 and J195).USH2A gene mutations were verified by Sanger sequencing and repetitive sequence mutations of USH2A were detected by fluorescent quantitative PCR.Re-sults The two probands had moderate to severe hearing loss.Compound heterozygous mutation of USH2A c.8559-2A＞G(splicing)and USH2A c.dup(exon37-39)were determined to be the causative mutations in the J193 family;while compound heterozygous mutation of USH2A c.9570+1G＞A(splicing)and USH2A c.5581G＞A(p.G1861S)likely the causative mutations in the J1 95 family.Conclusion The target region capture technology combined with next genera-tion sequencing provides a powerful tool for the detection for deaf individuals and families with a high degree of genetic heterogeneity.This method was successfully used to identify deafness gene mutations for the two families in the current study.While USH2A c.8559-2A＞G,USH2A c.9570+1G＞A,and USH2A c.5581G＞A(p.G1861S)are known deafness mutations,USH2A c.dup(exon37-39)is the first reported large segment repeat insertion pathogenic mutation,an addi-tion to the mutation types and patterns of hereditary deafness.关键词
USH2A基因/大片段重复突变/常染色体隐性遗传性耳聋Key words
USH2A/large fragment duplication mutation/autosomal recessive hereditary hearingloss分类
医药卫生引用本文复制引用
许军,林妘,杨涛..USH2A基因大片段重复等突变导致中重度听力损失[J].中华耳科学杂志,2023,21(6):876-881,6.基金项目
国家自然科学基金(82271157) （82271157）
上海市耳鼻疾病转化医学重点实验室资助项目(14DZ2260300)National Science Foundation of China(82271157) （14DZ2260300）
Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases(14DZ2260300) （14DZ2260300）
