Whole‐Exome Sequencing Identifies a Variant in TMEM132E Causing Autosomal‐Recessive Nonsyndromic Hearing Loss DFNB99 |
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| Authors: | Jiangxia Li 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 |
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| Institution: | 1. Key Laboratory for Experimental Teratology of the Ministry of Education and Department of Medical Genetics, Shandong University School of Medicine, Jinan, Shandong, China;2. School of Life Science, Shandong University, Jinan, Shandong, China;3. Institute of Otolaryngology, Chinese PLA General Hospital, Beijing, China;4. BGI‐Shenzhen, Shenzhen, China |
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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 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. |
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| Keywords: | ARNSHL DFNB99 TMEM132E inner hair cell whole‐exome sequencing |
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