PUBLICATION
Whole-exome Sequencing Identifies a Variant in TMEM132E Causing Autosomal-Recessive Nonsyndromic Hearing Loss DFNB99
- Authors
- Li, J., Zhao, X., Xin, Q., Shan, S., Jiang, B., Jin, Y., Yuan, H., Dai, P., Xiao, R., Zhang, Q., Xiao, J., Shao, C., Gong, Y., Liu, Q.
- ID
- ZDB-PUB-141022-7
- Date
- 2015
- Source
- Human Mutation 36(1): 98-105 (Journal)
- Registered Authors
- Keywords
- ARNSHL, DFNB99, TMEM132E, inner hair cell, whole exome sequencing
- MeSH Terms
-
- Animals
- China
- Chromosomes, Human, Pair 15/genetics
- Deafness/genetics
- Exome
- Gene Knockdown Techniques
- Genes, Recessive
- Hair Cells, Auditory, Inner/metabolism*
- Humans
- Male
- Membrane Proteins/genetics*
- Membrane Proteins/metabolism*
- Mice
- Mutation, Missense
- Pedigree
- Sequence Analysis, DNA/methods*
- Zebrafish
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- PubMed
- 25331638 Full text @ Hum. Mutat.
Citation
Li, J., Zhao, X., Xin, Q., Shan, S., Jiang, B., Jin, Y., Yuan, H., Dai, P., Xiao, R., Zhang, Q., Xiao, J., Shao, C., Gong, Y., Liu, Q. (2015) Whole-exome Sequencing Identifies a Variant in TMEM132E Causing Autosomal-Recessive Nonsyndromic Hearing Loss DFNB99. Human Mutation. 36(1):98-105.
Abstract
Autosomal recessive non-syndromic 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. This article is protected by copyright. All rights reserved.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping