金华地区妊娠早期孕妇耳聋相关基因筛查分析

Screening and analysis of deafness-associated genes in early pregnant women in Jinhua area

目的 分析金华地区孕妇耳聋基因变异位点分布类型及携带率,了解金华地区妊娠早期女性耳聋基因变异类型和分布情况。方法 选取2017年9月—2021年10月来金华市妇幼保健院就诊的3 389名孕妇,采用18个基因100个位点高通量测序技术,检出为变异位点携带者的,召回其配偶进行耳聋相关基因测序,并给予遗传咨询和生育指导。对6个有耳聋家族史的家系,采用227个基因Panel测序,同时深入了解其家系成员的听力情况。结果 纳入研究的3 389名孕妇中,共检出224名孕妇携带耳聋基因变异,总携带率为6.61%。213名孕妇携带1个耳聋基因变异位点,对应的基因分别为GJB2(103例,3.04%)、SLC26A4(65例,1.92%)、GJB3(13例,0.38%)、MT-CO1(19例,0.56%)、MT-RNR1(13例,0.38%);11名孕妇同时携带2个基因的变异位点。不同变异位点的检出率各不相同,在GJB2基因中c.235delC位点检出率最高(71例,2.10%),其次是SLC26A4基因IVS7-2A>G位点(35例,1.03%)。63名携带者孕妇的配偶接受了耳聋基因检测,发现4名为耳聋基因携带者,其中1名与孕妇携带相同的致病基因位点GJB2 c.235delC。对6个耳聋家系进行检测,4个家系主要为GJB2变异造成,1个家系为SLC26A4变异造成,1个家系为LOXHD1变异造成。结论 对孕妇群体以及有明确耳聋家族史的家庭进行耳聋基因变异位点携带者检测,有助于了解金华地区的常见耳聋基因携带情况,并为受检者提供生育指导。

Objective To analyze the distribution types and carrier rates of hearing loss gene mutation sites in pregnant women in Jinhua area,and understand the types and distribution of hearing loss genes in early pregnant women in Jinhua area.Methods A total of 3389 pregnant women who visited Jinhua Maternal&Child Health Care Hospital from September 2017 to October 2021 were screened using high-throughput sequencing atl00 loci of18genes.Ifthe results were heterotopic carriers,their spouses were recalled for sequencing of deafness related genes,then genetic counseling and fertility guidance were provided.The family members in 6 families with hearing impairment were detected using 227 gene Panel sequencing to understand the hearing status.Results A total of 3389 pregnant women were screned,and 224 pregnant women were found to cary hearing loss genes variants,with a total carrier rate of 6.61%.A total of 213 pregnant women were detected to carry one deafness gene mutation site,including GJB2(103 cases,3.04%),SLC26A4(65 cases,1.92%),GJB3(13 cases,0.38%),MT-CO1(19 cases,0.56%),and MT-RNRI(13 cases,0.38%).Eleven pregnant women carried two variants in two genes simultaneously.The detection rates of different variation loci were different,the detection rate of c.235delC locus in GJB2 gene was the highest(71 cases,2.09%),followed by IVS7-2A>G locus in SLC26A4 gene(35 cases,1.03%).The spouses of 63 carrier pregnant women were tested for hearing loss genes variants,and4cases of them were carriers,including one case carried the same pathogenic gene variant GJB2 c.235delC as the pregnant woman.Six families with deafness were detected,of which four mutations were mainly caused by GJB2 mutation,one mutation was caused by SLC26A4 mutation,and one mutation was caused by LOXHD1 gene mutation.Conclusion Detection of deafness gene variants in pregnant women and families with a clear family history of deafness is helpful to understand the carriage of common deafness genes in Jinhua area and provide fertility guidance for the tested patients.