title: Whole-exome sequencing identifies a variant in TMEM132E causing autosomal-recessive nonsyndromic hearing loss DFNB99.
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.
authors.affiliation: Key Laboratory for Experimental Teratology of the Ministry of Education and Department of Medical Genetics, Shandong University School of Medicine, Jinan, Shandong, 250012, China.
authors.forename: Jiangxia
authors.initials: J
authors.lastname: Li
authors.forename: Xiaohan
authors.initials: X
authors.lastname: Zhao
authors.forename: Qian
authors.initials: Q
authors.lastname: Xin
authors.forename: Shan
authors.initials: S
authors.lastname: Shan
authors.forename: Baichun
authors.initials: B
authors.lastname: Jiang
authors.forename: Yecheng
authors.initials: Y
authors.lastname: Jin
authors.forename: Huijun
authors.initials: H
authors.lastname: Yuan
authors.forename: Pu
authors.initials: P
authors.lastname: Dai
authors.forename: Ruo
authors.initials: R
authors.lastname: Xiao
authors.forename: Qingyan
authors.initials: Q
authors.lastname: Zhang
authors.forename: Jingjing
authors.initials: J
authors.lastname: Xiao
authors.forename: Changshun
authors.initials: C
authors.lastname: Shao
authors.forename: Yaoqin
authors.initials: Y
authors.lastname: Gong
authors.forename: Qiji
authors.initials: Q
authors.lastname: Liu
mesh_terms: D000818:Animals; D002681:China; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics; D003638:Deafness / Q000235:genetics; D059472:Exome; D055785:Gene Knockdown Techniques; D005808:Genes, Recessive; D006199:Hair Cells, Auditory, Inner / Q000378:metabolism*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D020125:Mutation, Missense; D010375:Pedigree; D017422:Sequence Analysis, DNA / Q000379:methods*; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D008565:Membrane Proteins; C000601104:TMEM132E protein, human; D029961:Zebrafish Proteins
keywords: ARNSHL; DFNB99; TMEM132E; inner hair cell; whole-exome sequencing