The homozygous p.V37I variant of GJB2 is associated with diverse hearing phenotypes
The homozygous p.V37I variant of GJB2 is associated with diverse hearing phenotypes
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GJB2 纯合 p.V37I 变体与不同的听力表型相关
DOI：
10.1111/cge.12387
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发表时间：
2015-04-01
影响因子：
3.5
通讯作者：
Yang, T.
中科院分区：
文献类型：
--
作者：
Chai, Y.;Chen, D.;Yang, T.
GJB 2的纯合子p.V37I变体在东亚人中常见，并且据报道在轻度至中度听力损伤（HI）中具有致病作用。在这项研究中，我们调查了三个中国汉族队列中的纯合子p.V37I的患病率和表型谱，其中重度至重度HI（n=857，队列S），轻度至中度HI（n=88，队列M）和听力正常（n=1550，队列N）。GJB 2测序显示，在队列S、M和N中分别在1.63%（14/857）、12.5%（11/88）和0.32%（5/1550）的受试者中检测到纯合子p.V37I。它与轻度至中度（p=2.0x10（-11））和重度至极重度（p=0.001）HI密切相关，但估计具有相当低的潜伏期（17%）。在携带纯合p.V37I的听力受损受试者中，65%（11/17）的HI发病是先天性的，35%（6/17）的HI发病是延迟的。通过对79个已知耳聋基因进行靶向下一代测序，我们在队列S的14例p.V37I纯合子受试者中的1例中发现了额外的CDH 23纯合子致病突变。我们的研究表明，纯合子p.V37I与比以前揭示的更广泛的听力表型相关。本研究提供的数据可有效地应用于该变异携带者的临床评估和遗传咨询。
The homozygous p.V37I variant of GJB2 is frequent in East Asians and has been reported to have a pathogenic role in mild-to-moderate hearing impairment (HI). In this study, we investigated the prevalence and phenotypic spectrum of homozygous p.V37I in three Chinese Han cohorts with severe-to-profound HI (n=857, Cohort S), mild-to-moderate HI (n=88, Cohort M) and normal hearing (n=1550, Cohort N). Sequencing of GJB2 showed that homozygous p.V37I was detected in 1.63% (14/857), 12.5% (11/88) and 0.32% (5/1550) of subjects in Cohorts S, M and N, respectively. It was strongly associated with both mild-to-moderate (p=2.0x10(-11)) and severe-to-profound (p=0.001) HI, but was estimated to have a rather low penetrance (17%). Among the hearing impaired subjects with homozygous p.V37I, the onset of HI was congenital in 65% (11/17) and delayed in 35% (6/17). By targeted next-generation sequencing of 79 known deafness genes, we identified an additional homozygous pathogenic mutation of CDH23 in 1 of 14 p.V37I homozygous subjects from Cohort S. Our study suggested that homozygous p.V37I is associated with a broader spectrum of hearing phenotypes than previously revealed. Data presented in this study can be effectively applied to clinical evaluation and genetic counseling of people carrying this variant.