142例GJB2双等位基因突变患儿基因型与听力表型的差异分析

Analysis of the difference between genotype and hearing phenotype in 142 infants with biallelic allele variant in GJB2

目的分析GJB2双等位基因突变患儿不同基因型的听力表型差异,为临床提供参考。方法2012年8月~2024年3月在首都医科大学附属北京同仁医院确诊为GJB2双等位基因突变患儿142例,所有患儿均接受新生儿听力筛查、耳聋基因筛查及听力诊断检查。根据突变位点类型分为三组,分别为T/T组(截断/截断突变,59例)、T/NT组(截断/非截断突变,50例)及NT/NT组(非截断/非截断突变,33例),分析三组基因型、新生儿听力筛查结果、首诊月龄及听力诊断结果。结果T/T组基因型以c.235delC/c.235delC为主(57.63%),T/NT组以c.235delC/c.109G>A为主(74.00%),NT/NT组以c.109G>A/c.109G>A为主(96.97%)。新生儿听力筛查未通过率为80.28%,其中T/T组未通过率89.83%,显著高于T/NT组70.00%(P=0.009)。首诊月龄为(3.70±1.56)个月,三组差异无统计学意义(P>0.05)。142例中,确诊听力损失104例(73.24%),听力正常38例(26.76%);T/T组听力损失占比100.00%,显著高于T/NT组52.00%(P<0.001)及NT/NT组57.58%(P<0.001)。听力损失侧别,104例中,双侧听力损失86例(82.69%),单侧听力损失18例(17.31%);T/T组双侧听力损失占比100.00%,显著高于T/NT组57.69%(P<0.001)及NT/NT组63.16%(P<0.001)。听力损失104例(190耳)中,听力损失程度以轻度至中度为主(63.16%),其次为极重度(24.74%)及重度(12.10%)。其中T/T组以重度至极重度听力损失为主(58.47%),T/NT组及NT/NT组均以轻度听力损失为主(58.54%及74.19%),差异具有统计学意义(P<0.001)。结论本研究T/T组所有患儿首诊均确诊为双侧听力损失,以重度及极重度听力损失为主;T/NT组及NT/NT组首诊确诊双侧或单侧听力损失分别为52.00%及57.58%,以轻度听力损失为主。

OBJECTIVE To analyze the difference of genotypes and hearing phenotypes in infants with biallelic allele variant in GJB2,and to provide reference for clinical practice.METHODS One hundred and forty-two subjects with biallelic allele variant in GJB2 were recruited in Beijing Tongren Hospital from August 2012 to March 2024.All subjects received universal newborn hearing screening(UNHS),neonatal deafness genetic screening and audiological tests.The subjects were divided into three groups according to the genotypes:T/T groups(truncated/truncated mutations,59 cases),T/NT group(truncated/non-truncated mutations,50 cases)and NT/NT group(non-truncated/non-truncated mutations,33 cases).Three groups of genotypes,newborn hearing screening results,age at first diagnosis and hearing diagnosis results were analyzed.RESULTS The homozygous mutation of c.235delC/c.235delC was the dominant in T/T group(57.63%),the compound heterozygous mutation of c.235delC/c.109G>A was the dominant in T/NT group(74.00%),and the homozygous mutation of c.109G>A/c.109G>A was the dominant in NT/NT group(96.97%).The overall refer rate of UNHS was 80.28%,and the refer rate of T/T group was 89.83%,which was significantly higher than that of T/NT group 70.00%(P=0.009).The age of first diagnosis of 142 cases was(3.70±1.56)months,there was no significant difference between the three groups(P>0.05).In 142 cases,104 cases with hearing loss accounted for 73.24%,38 cases with normal hearing accounted for 26.76%.The proportion of confirmed hearing loss in T/T group was 100.00%,which was significantly higher than that in T/NT group 52.00%(P<0.001)and NT/NT group 57.58%(P<0.001).In side of hearing loss,of the 104 patients with hearing loss,86 cases(82.69%)had bilateral hearing loss and 18 cases(17.31%)had unilateral hearing loss.The proportion of bilateral hearing loss in T/T group was 100.00%,which was significantly higher than that in T/NT group 57.69%(P<0.001)and NT/NT group 63.16%(P<0.001).Among 190 ears of 104 patients with hearing loss,the degree of hearing loss was predominantly mild to moderate(63.16%),followed by profound(24.74%)and severe(12.10%).Among them,the T/T group was mainly marked by severe to profound hearing loss(58.47%),while both the T/NT group and the NT/NT group were mainly characterized by mild hearing loss(58.54%and 74.19%),and the differences among the three groups were statistically significant(P<0.001).CONCLUSION In the T/T group,all patients were diagnosed as bilateral hearing loss at first diagnosis,and was mainly severe and profound hearing loss.The bilateral and unilateral hearing loss were 52.00%and 57.58%in the T/NT group and NT/NT group at first diagnosis respectively,and was mainly mild hearing loss.