摘要
目的对广东人群遗传性非综合征型耳聋热点基因突变筛查、基因诊断和出生缺陷临床防控模式进行初步探索,并提供人群频率、基因诊断方案等数据依据。方法应用遗传性耳聋基因芯片对46587名正常听力且无耳聋家族史的育龄女性进行耳聋基因热点突变筛查,对携带者配偶进行相应基因的Sanger测序,对非综合征型耳聋患者采用基因芯片结合GJB2、SLC26A4基因测序。对相同致病基因携带者知情选择产前诊断。结果46587例广东地区正常听力且无耳聋家族史的育龄女性遗传性耳聋热点突变携带率为3.40%,其中GJB2、SLC26A4、GJB3、线粒体MT-RNR1基因在人群携带率分别为1.88%、1.17%、0.14%、0.19%;694例非综合征型耳聋患者中,共检测到78种变异,其中2个未见报道变异根据ACMG分类指南可分为可能致病变异。共计为170例孕妇知情选择进一步产前诊断,其中25例孕妇因选择终止妊娠。结论本研究对广东人群遗传性耳聋热点突变筛查、基因诊断以及出生缺陷临床防控模式进行大样本的探索,丰富了非综合征耳聋基因突变谱,为耳聋基因突变筛查、耳聋基因诊断及遗传咨询提供了重要数据资料。
Objective To study the implication of genetic screening,diagnosis and clinical prevention programs in non-syndromic hereditary hearing loss and provide data basis of population frequency and genetic diagnosis strategy in Guangdong population.Methods The chip with nine hotspot mutations of hereditary hearing loss gene was applied in 46,587 women of childbearing age with normal hearing and without family history of hearing loss.Sanger sequencing tests were provided to the spouses of carriers.Chip combined with GJB2 and SLC26A4 gene sequence analyses were applied to the patients with hearing loss.Couples with high risk were referred to take prenatal diagnosis with informed consent.Results The carrier rate among the 46587 normal hearing women with negative family history of hearing loss was 3.40%,and the rate of mutations of the GJB2,SLC26A4,GJB3 and MT-RNR1 genes was 1.88%,1.17%,0.14%and 0.19%respectively.Among the 694 non-syndromic hearing loss patients,we found 78 variants,including 2 disease-related variants not previously reported in the ACMG.A total of 170 pregnant women consented to further prenatal diagnosis,of whom 25 chose to terminate their pregnancy.Conclusion In this study,we explored a large-scale sample of screening,diagnosis and clinical prevention models of hereditary hearing loss in Guangdong population.This work also enriched the gene mutation spectrum of non-syndromic hearing loss and provided important data for screening,diagnosis and genetic counseling in hereditary hearing loss.
作者
刘玲
曾玉坤
丁红珂
姚翠泽
余丽华
刘畅
张彦
LIU Ling;ZENG Yukun;DING Hongke;YAO Cuize;YU Lihua;LIU Chang;ZHANG Yan(Center of Medical Genetics,Guangdong Women and Children Hospital,Guangzhou,Guangdong,China,511400)
出处
《中华耳科学杂志》
CSCD
北大核心
2019年第5期625-631,共7页
Chinese Journal of Otology
关键词
出生缺陷
非综合征型耳聋
基因检测
Birth Defect
Non-syndromic Hereditary Hearing Loss
Gene Test
