Department of Cellular Biology and Genetics, Hunan Provincial Key Laboratory of Dong Medicine, Hunan University of Medicine.
Biosci Trends. 2018;12(5):470-475. doi: 10.5582/bst.2018.01156.
Autosomal recessive (AR) non-syndromic hearing loss (NSHL) is the most common form of hereditary deafness. Mutations in the gap junction protein beta 2 (GJB2) gene encoding connexin 26 (Cx26) account for about 50% of cases of ARNSHL. In the current study, a combination of exome sequencing and Sanger sequencing in a Chinese Dong family with ARNSHL allowed identification of a novel compound heterozygous mutation c.240G>C(p. Q80H)/C.109G>A(p.V37I) in exon 2 of the GJB2 gene, which co-segregated with the disease phenotype in this family and was not evident in 100 healthy controls. Bioinformatic analysis revealed that the two mutations in the GJB2 gene were probably pathogenic. Results indicated that the compound heterozygous variants, p.Q80H and p.V37I, in the GJB2 gene are associated with ARNSHL. The Q80H variant was initially identified in patients of Dong Chinese origin with NSHL. The current results broaden the spectrum of GJB2 mutations responsible for NSHL and have important implications for molecular diagnosis, treatment, and genetic counseling for this family.
常染色体隐性（AR）非综合征性听力损失（NSHL）是遗传性耳聋最常见的形式。编码连接蛋白 26（Cx26）的缝隙连接蛋白β 2（GJB2）基因突变约占 ARNSHL 的 50%。在本研究中，对一个具有 ARNSHL 的中国侗族家庭进行外显子组测序和 Sanger 测序的组合分析，鉴定出 GJB2 基因外显子 2 中一种新的复合杂合突变 c.240G>C(p. Q80H)/C.109G>A(p.V37I)，该突变与该家系中的疾病表型共分离，在 100 名健康对照中未发现。生物信息学分析表明，GJB2 基因中的两个突变可能是致病的。结果表明，GJB2 基因中的复合杂合变体 p.Q80H 和 p.V37I 与 ARNSHL 相关。Q80H 变体最初在患有 NSHL 的侗族患者中被发现。目前的结果拓宽了导致 NSHL 的 GJB2 突变谱，对该家系的分子诊断、治疗和遗传咨询具有重要意义。
