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The frequency of the pathogenic allele of the autosomal recessive deafness gene GJB2 varies among different populations in the world, and accumulates to a sufficiently high frequency in certain population. The purpose of this study is to investigate the origin and evolution of GJB2 pathogenic alleles in Chinese deaf patients. Children with non‐syndromic hearing loss, and their parents, from 295 families were recruited. Customized capture probes targeted at 943 single nucleotide polymorphisms (SNPs) related to GJB2 gene were designed for sequencing of genomic DNA in blood samples. Haplotypes carrying pathogenic allele were analyzed through linkage disequilibrium block building, ancestry tracing, and extended haplotype heterozygosity calculation. Two pathogenic GJB2 alleles, c.235delC (18.41%) and c.109G > A (15.57%), were observed in 867 donors. For c.235delC allele, three different core haplotypes with one major haplotype (97.32%) were found, and their core SNPs were 100% conserved. For c.109G > A allele, six different haplotypes with one major haplotype (93.28%) were found and the major c.109G > A allele evolved from a specific ancestral haplotype. Geographical origins of donors carrying GJB2 c.109G > A and c.235delC core haplotypes centered between Qinghai and Neimenggu. GJB2 c.235delC has long‐range linkage disequilibrium. No positive selection signature was found for GJB2 c.235delC or c.109G > A in the studied population. In conclusion, we discovered a single origin of GJB2 c.235delC allele and multiple independent origins of GJB2 c.109G > A allele. Alternative to positive selection or multiple independent recurrent mutation event, population bottleneck effect might account for the observed high population frequency of these pathogenic alleles. [ABSTRACT FROM AUTHOR]

Aim: Autosomal dominant non‐syndromic hearing loss is a common sensorineural disorder with extremely high genetic heterogeneity. CEA antigen‐related cell adhesion molecule 16(CEACAM16)is a secreted glycoprotein encoded by the CEACAM16 gene. Mutations in CEACAM16 lead to autosomal dominant non‐syndromic hearing loss in humans, due defects in the tectorial membrane of the inner ear. Here we reported a novel missense variant in CEACAM16 gene causes autosomal dominant non‐syndromic hearing loss. Material and methods: A four‐generation Chinese family affected by late‐onset and progressive hearing loss was enrolled in this study. The proband was analyzed by targeted next‐generation sequencing and bioinformatic analysis. And in vitro experiments were performed in overexpressed transfected HEK293T cells to investigate the pathogenesis of the mutant protein. Results: We identified a novel missense variant in the CEACAM16 gene c.763A>G; (p.Arg255Gly) as causing autosomal dominant non‐syndromic hearing loss in the Chinese family. Using Western blot analysis, ELISA, and immunofluorescence we found increased expression level of the secreted mutant CEACAM16 protein, both intracellularly and extracellularly, compared with wild type CEACAM16 protein. Conclusion: Our study showed that the p.Arg255Gly variant leads to increased secretion of mutant CEACAM16 protein, with potential deleterious effect to the function of the protein. Our findings expand the mutation spectrum of CEACAM16, and further the understanding CEACAM16 function and implications in disease. [ABSTRACT FROM AUTHOR]

The "sandwich method" using a superior temporal fascia flap, auricle cartilage and a deep temporal muscle flap can repair the defect in the posterior wall of the ear canal and cover the electrode. Of the 45 cases of cochlear implantation failure identified, 14 involved revision surgery without reimplantation, and 31 cases required reimplantation (26 ipsilateral and 5 contralateral; Table). In one patient with skin flap necrosis and incorrectly positioned implant, revision surgery was performed to clean the wound, repair the flap and adjust the position of the implant (Figure B). Revision surgery in the patients with skin flap necrosis revealed implant protrusion in all patients and an incorrectly positioned implant in one patient. [Extracted from the article]