Chen Kaitian, Wu Xuan, Zong Ling, Jiang Hongyan
Department of Otorhinolaryngology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Institute of Otorhinolaryngology, Sun Yat-sen University, Guangzhou, China.
J Clin Lab Anal. 2018 Nov;32(9):e22592. doi: 10.1002/jcla.22592. Epub 2018 Jun 21.
Genetic analysis detected excessive mono-allelic recessive GJB2 mutations in individuals with idiopathic deafness; the remaining alleles in trans/cis are underdetermined. The aim of this study was to assess the contributions of variants in GJB3 or GJB6 to non-syndromic sensorineural hearing impairment (NSHI) in Chinese patients with mono-allelic GJB2 mutations.
The entire coding sequences of GJB3/GJB6, as well as deletions in GJB6, in a cohort of NSHI patients (n = 100) carrying likely pathogenic heterozygous GJB2 mutations, were tested. Targeted next generation sequencing was further performed in a multiplex family GDHY with moderate to profound NSHI.
Putatively causative GJB3 variant underlied 1% (1/100) in this cohort. In family GDHY, we identified a rare GJB3 c.250G>A mutation, as double heterozygotes with GJB2 c.109G>A and/or a novel GJB2 mutation c.638T>C predicted to be damaging in a digenic inheritance after precluding other attributable mutations from 127 deafness genes. No GJB6 mutation was found.
GJB3/GJB6 variants account for a low proportion in autosomal recessive GJB2 mutation carriers in our cohort. Environmental causes, or other NSHI relevant genes, revealed by targeted next generation sequencing or whole exome sequencing, may play major roles in triggering deafness in these patients.
基因分析在特发性耳聋患者中检测到过多的单等位基因隐性GJB2突变；反式/顺式中的其余等位基因尚不确定。本研究的目的是评估GJB3或GJB6变异对携带单等位基因GJB2突变的中国非综合征性感音神经性听力损失（NSHI）患者的贡献。
对一组携带可能致病的杂合GJB2突变的NSHI患者（n = 100）进行GJB3/GJB6的完整编码序列以及GJB6中的缺失检测。对中度至重度NSHI的多重家系GDHY进一步进行靶向二代测序。
在该队列中，推定致病的GJB3变异占1%（1/100）。在GDHY家系中，我们鉴定出一个罕见的GJB3 c.250G>A突变，作为与GJB2 c.109G>A和/或一个新的GJB2突变c.638T>C的双重杂合子，在排除127个耳聋基因的其他可归因突变后，预测其在双基因遗传中具有损害性。未发现GJB6突变。
在我们的队列中，GJB3/GJB6变异在常染色体隐性GJB2突变携带者中占比很低。靶向二代测序或全外显子组测序揭示的环境因素或其他与NSHI相关的基因，可能在引发这些患者耳聋方面起主要作用。
