Unveiling a novel GJB2 dominant K22T mutation in a Chinese family with hearing loss  

作　　者：Haiting Ji Yilai Shu Huawei Li 

机构地区：[1]Department of the Affiliated Eye and ENT Hospital,State Key Laboratory of Medical Neurobiology,ENT Institute and Otorhinolaryngology,Fudan University,Shanghai 200031,China [2]NHC Key Laboratory of Hearing Medicine,Fudan University,Shanghai 200031,China [3]Shanghai Engineering Research Centre of Cochlear Implant,Shanghai 200031,China [4]ENT Institute and Otorhinolaryngology Department of Eye & ENT Hospital,State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science,Fudan University,Shanghai 200031,China [5]Institutes of Biomedical Sciences,Fudan University,Shanghai 200032,China

出　　处：《Acta Biochimica et Biophysica Sinica》2024年第6期945-951,共7页生物化学与生物物理学报（英文版）

基　　金：supported by the grants from the National Natural Science Foundation of China(Nos.81600816 and 82192860);the Original Scientific Research Supporting Program of Fudan University,Shanghai Municipal Key Clinical Specialty(No.shslczdzk00801);the Shanghai Science and Technology Committee(Shanghai Clinical Medical Research Center for Otorhinolaryngology)(No.20MC1920200).

摘　　要：Hearing loss constitutes one of the most prevalent conditions within the field of otolaryngology.Recent investigations have revealed that mutations in deafness-associated genes,including point mutations and variations in DNA sequences,can cause hearing impairments.With the ethology of deafness remaining unclear for a substantial portion of the affected population,further screenings for pathogenic mutations are imperative to unveil the underlying mechanisms.On this study,by using next-generation sequencing,we examine 129 commonly implicated deafness-related genes in a Chinese family with hearing loss,revealing a novel heterozygous dominant mutation in the GJB2 gene(GJB2:c.65T>G:p.Lys22Thr).This mutation consistently occurs in affected family members but is not detected in unaffected individuals,strongly suggesting its causative role in hearing loss.Structural analysis indicates potential disruption to the Cx26 gap junction channel’s hydrogen bond and electrostatic interactions,aligning with predictions from the PolyPhen and SIFT algorithms.In conclusion,our study provides conclusive evidence that the identified heterozygous GJB2 mutation(GJB2:c.65T>G:p.Lys22Thr),specifically the K22T alteration,is the primary determinant of the family’s deafness.This contribution enhances our understanding of the interplay between common deafness-associated genes and hearing loss,offering valuable insights for diagnostic guidance and the formulation of therapeutic strategies for this condition.

关 键 词：DEAFNESS point mutations GJB2 next-generation sequencing 

分 类 号：R764[医药卫生—耳鼻咽喉科]