2. Academic Validation
  3. Whole-exome sequencing identifies a variant in TMEM132E causing autosomal-recessive nonsyndromic hearing loss DFNB99

Whole-exome sequencing identifies a variant in TMEM132E causing autosomal-recessive nonsyndromic hearing loss DFNB99

  • Hum Mutat. 2015 Jan;36(1):98-105. doi: 10.1002/humu.22712.
Jiangxia Li 1,  Xiaohan Zhao,  Qian Xin,  Shan Shan,  Baichun Jiang,  Yecheng Jin,  Huijun Yuan,  Pu Dai,  Ruo Xiao,  Qingyan Zhang,  Jingjing Xiao,  Changshun Shao,  Yaoqin Gong,  Qiji Liu
Affiliations

Affiliation

  • 1 Key Laboratory for Experimental Teratology of the Ministry of Education and Department of Medical Genetics, Shandong University School of Medicine, Jinan, Shandong, 250012, China.
PMID: 25331638 DOI: 10.1002/humu.22712
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 showed Tmem132e highly expressed in murine inner hair cells. Furthermore, knockdown of the tmem132e ortholog in zebrafish affected the mechanotransduction of hair cells. Finally, wild-type human TMEM132E mRNA, but not the mRNA carrying the c.1259G>A mutation rescued the Tmem132e knockdown phenotype. We conclude that the variant in TMEM132E is the most likely cause of DFNB99.

Keywords

ARNSHL; DFNB99; TMEM132E; inner hair cell; whole-exome sequencing.

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