Whole-Exome Sequencing Identifies a Variant inTMEM132ECausing Autosomal-Recessive Nonsyndromic Hearing Loss DFNB99

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Abstract

Autosomal-recessive nonsyndromic hearing loss (ARNSHL) features a high degree of genetic heterogeneity. Many genes responsible for ARNSHL have been identified or mapped. We previously mapped an ARNSHL locus at 17q12, herein designated DFNB99, in a consanguineous Chinese family. In this study, whole-exome sequencing revealed a homozygous missense mutation (c.1259G>A, p.Arg420Gln) in the gene-encoding transmembrane protein 132E (TMEM132E) as the causative variant. Immunofluorescence staining of the Organ of Corti showedTmem132ehighly expressed in murine inner hair cells. Furthermore, knockdown of thetmem132eortholog in zebrafish affected the mechanotransduction of hair cells. Finally, wild-type humanTMEM132EmRNA, but not the mRNA carrying the c.1259G>A mutation rescued theTmem132eknockdown phenotype. We conclude that the variant inTMEM132Eis the most likely cause of DFNB99.

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