新生儿非综合征型听力损失GJB2基因的突变分析

目的探讨新生儿听力筛查确诊的听力损失与GJB2基因突变的关系。方法应用耳声发射及听觉诱发电位等方法确诊先天性双耳重度极重度非综合征型听力损失患儿20例,采用聚合酶链反应和基因测序等技术检测GJB2基因的编码区序列。50名听力正常人群作对照组。结果3例患儿的基因型为235delC/235delC,占15%;1例为235delC/299300delAT;1例为235delC/605ins46,605ins46是首次在中国人群中发现的新突变;1例为235delC等位基因携带者。即在所分析的患儿中,5例与GJB2基因突变有关,占25%。235delC等位基因频率对照组为1%,患儿组为22.5%(P<0.01)。此外,在耳聋患者和正常人群中尚存在V27I,V37I、E114G、T123N等多态性改变。结论GJB2基因突变是引起听力损失发生的重要因素;235delC是GJB2基因的主要致病突变位点,同时存在特殊类型的新突变以及较多形式的多态性。

Mutations of GJB2 gene in infants with non-syndromic hearing impairment

Objective To explore the relationship between GJB2 gene mutations and severe-to-profound bilateral non-syndromic hearing impairment (NSHI). Methods Peripheral blood was collected from 20 infants with severe-to-profound bilateral NSHI confirmed by otoacoustic emissions (OAE), auditory brainstem responses (ABR) and clinical physical examination, 11 male and 9 female, aged 3 months to 3 years. PCR and sequencing technique were used to analyze the coding region of GJB2 gene. Fifty persons with normal hearing, 25 males and 25 female, aged 20~50, all without family history of hearing impairment, were used as controls. Results Three infants (15%) were identified as 235delC/235delC homozygotes; one infant was identified as 235delC/299-300delAT compound heterozygote; one was identified as 235delC heterozygote; and one as 235delC/605ins46 compound heterozygote with 605ins46 mutation, a novel mutation reported in Chinese for the first time. GJB2 gene mutations were found in 5 NSHI infants (25%). The allelic frequency of 235delC allele was 22.5% in the NSHI infants and 1% in the control group (P<0.01). Besides, multiple polymorphisms such as V27I,V37I,E114G,T123N were found in both the patients and controls. Conclusion GJB2 analysis is an important test for infants with severe-to-profound bilateral NSHI. 235delC is the main pathogenic mutation site in GJB2 gene.