Whole-Exome Sequencing Identifies a Variant in TMEM132E Causing Autosomal-Recessive Nonsyndromic Hearing Loss DFNB99

被引：32

作者：

Li, Jiangxia ^{[1
,2
]}

Zhao, Xiaohan ^{[1
,2
]}

Xin, Qian ^{[1
,2
]}

Shan, Shan ^{[1
,2
]}

Jiang, Baichun ^{[1
,2
]}

Jin, Yecheng ^{[3
]}

Yuan, Huijun ^{[4
]}

Dai, Pu ^{[4
]}

Xiao, Ruo ^{[5
]}

Zhang, Qingyan ^{[5
]}

Xiao, Jingjing ^{[5
]}

Shao, Changshun ^{[1
,2
]}

Gong, Yaoqin ^{[1
,2
]}

Liu, Qiji ^{[1
,2
]}

机构：

[1] Shandong Univ, Minist Educ, Key Lab Expt Teratol, Sch Med, Jinan 250012, Shandong, Peoples R China

[2] Shandong Univ, Sch Med, Dept Med Genet, Jinan 250012, Shandong, Peoples R China

[3] Shandong Univ, Sch Life Sci, Jinan 250012, Shandong, Peoples R China

[4] Chinese Peoples Liberat Army Gen Hosp, Inst Otolaryngol, Beijing 100853, Peoples R China

[5] BGI Shenzhen, Shenzhen 518083, Peoples R China

来源：

HUMAN MUTATION | 2015年 / 36卷 / 01期

基金：

中国国家自然科学基金;

关键词：

ARNSHL; DFNB99; TMEM132E; inner hair cell; whole-exome sequencing; LATERAL-LINE; PANIC DISORDER; HAIR-CELLS; ZEBRAFISH; PROTEIN; MUTATIONS; DEAFNESS; GENES;

D O I：

10.1002/humu.22712

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页码：98 / 105

页数：8

共 23 条

[1] A method and server for predicting damaging missense mutations
Adzhubei, Ivan A.
Schmidt, Steffen
Peshkin, Leonid
Ramensky, Vasily E.
Gerasimova, Anna
Bork, Peer
Kondrashov, Alexey S.
Sunyaev, Shamil R.
[J]. NATURE METHODS, 2010, 7 (04) : 248 - 249
[2] Cheng Lin, 2003, Zhonghua Yi Xue Yi Chuan Xue Za Zhi, V20, P89
[3] Defect in the gene encoding the EAR/EPTP domain-containing protein TSPEAR causes DFNB98 profound deafness
Delmaghani, Sedigheh
Aghaie, Asadollah
Michalski, Nicolas
Bonnet, Crystel
Weil, Dominique
Petit, Christine
[J]. HUMAN MOLECULAR GENETICS, 2012, 21 (17) : 3835 - 3844
[4] Hearing Loss: Mechanisms Revealed by Genetics and Cell Biology
Dror, Amiel A.
Avraham, Karen B.
[J]. ANNUAL REVIEW OF GENETICS, 2009, 43 : 411 - 437
[5] TMEM132D, a new candidate for anxiety phenotypes: evidence from human and mouse studies
Erhardt, A.
Czibere, L.
Roeske, D.
Lucae, S.
Unschuld, P. G.
Ripke, S.
Specht, M.
Kohli, M. A.
Kloiber, S.
Ising, M.
Heck, A.
Pfister, H.
Zimmermann, P.
Lieb, R.
Puetz, B.
Uhr, M.
Weber, P.
Deussing, J. M.
Gonik, M.
Bunck, M.
Kessler, M. S.
Frank, E.
Hohoff, C.
Domschke, K.
Krakowitzky, P.
Maier, W.
Bandelow, B.
Jacob, C.
Deckert, J.
Schreiber, S.
Strohmaier, J.
Noethen, M.
Cichon, S.
Rietschel, M.
Bettecken, T.
Keck, M. E.
Landgraf, R.
Mueller-Myhsok, B.
Holsboer, F.
Binder, E. B.
[J]. MOLECULAR PSYCHIATRY, 2011, 16 (06) : 647 - 663
[6] THE LATERAL-LINE AND INNER-EAR AFFERENTS IN LARVAL AND ADULT URODELES
FRITZSCH, B
[J]. BRAIN BEHAVIOR AND EVOLUTION, 1988, 31 (06) : 325 - 348
[7] FM1-43 dye behaves as a permeant blocker of the hair-cell mechanotransducer channel
Gale, JE
Marcotti, W
Kennedy, HJ
Kros, CJ
Richardson, GP
[J]. JOURNAL OF NEUROSCIENCE, 2001, 21 (18) : 7013 - 7025
[8] The transmembrane inner ear (Tmie) protein is essential for normal hearing and balance in the zebrafish
Gleason, Michelle R.
Nagiel, Aaron
Jamet, Sophie
Vologodskaia, Maria
Lopez-Schier, Hernan
Hudspeth, A. J.
[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2009, 106 (50) : 21347 - 21352
[9] Are TMEM genes potential candidate genes for panic disorder?
Gregersen, Noomi O.
Buttenschon, Henriette N.
Hedemand, Anne
Dahl, Hans A.
Kristensen, Ann S.
Clementsen, Birita
Woldbye, David P. D.
Koefoed, Pernille
Erhardt, Angelika
Kruse, Torben A.
Wang, August G.
Borglum, Anders D.
Mors, Ole
[J]. PSYCHIATRIC GENETICS, 2014, 24 (01) : 37 - 41
[10] Grhl2 deficiency impairs otic development and hearing ability in a zebrafish model of the progressive dominant hearing loss DFNA28
Han, Yanchao
Mu, Yu
Li, Xiaoquan
Xu, Pengfei
Tong, Jingyuan
Liu, Zhaoting
Ma, Tingting
Zeng, Guodong
Yang, Shuyan
Du, Jiulin
Meng, Anming
[J]. HUMAN MOLECULAR GENETICS, 2011, 20 (16) : 3213 - 3226

← 1 2 3 →