Mutations of LRTOMT, a fusion gene with alternative reading frames, cause nonsyndromic deafness in humans

被引：53

作者：

Ahmed, Zubair M. ^{[3
]}

Masmoudi, Saber ^{[4
]}

Kalay, Ersan ^{[1
,2
,5
]}

Belyantseva, Inna A. ^{[3
]}

Mosrati, Mohamed Ali ^{[4
]}

Collin, Rob W. J. ^{[1
,2
]}

Riazuddin, Saima ^{[3
]}

Hmani-Aifa, Mounira ^{[4
]}

Venselaar, Hanka ^{[6
]}

Kawar, Mayya N. ^{[3
]}

Tlili, Abdelaziz ^{[4
]}

van der Zwaag, Bert ^{[7
]}

Khan, Shahid Y. ^{[8
]}

Ayadi, Leila ^{[4
]}

Riazuddin, S. Amer ^{[8
]}

Morell, Robert J. ^{[3
]}

Griffith, Andrew J. ^{[9
]}

Charfedine, Ilhem ^{[10
]}

Caylan, Refik ^{[11
]}

Oostrik, Jaap ^{[1
]}

Karaguzel, Ahmet ^{[5
]}

Ghorbel, Abdelmonem ^{[10
]}

Riazuddin, Sheikh ^{[8
]}

Friedman, Thomas B. ^{[3
]}

Ayadi, Hammadi ^{[4
]}

Kremer, Hannie ^{[1
,12
,13
]}

机构：

[1] Radboud Univ Nijmegen, Med Ctr, Dept Otorhinolaryngol, NL-6500 HB Nijmegen, Netherlands

[2] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6500 HB Nijmegen, Netherlands

[3] Natl Inst Deafness & Other Commun Disorders, Mol Genet Lab, Rockville, MD 20850 USA

[4] Ctr Biotechnol, Unite Cibles Diagnost & Therapie, Sfax 3018, Tunisia

[5] Karadeniz Tech Univ, Fac Med, Dept Med Biol, TR-61080 Trabzon, Turkey

[6] Radboud Univ Nijmegen, Ctr Mol & Biomol Informat, NL-6500 HB Nijmegen, Netherlands

[7] Univ Med Ctr Utrecht, Rudolf Magnus Inst Neurosci, Dept Neurosci & Pharmacol, NL-3584 CG Utrecht, Netherlands

[8] Univ Punjab, Natl Ctr Excellence Mol Biol, Lahore 53700, Pakistan

[9] Natl Inst Deafness & Other Commun Disorders, Otolaryngol Branch, Rockville, MD 20850 USA

[10] CHU Habib Bourguiba Sfax, Serv ORL, Sfax 3029, Tunisia

[11] Karadeniz Tech Univ, Fac Med, Dept Otorhinolaryngol, TR-61080 Trabzon, Turkey

[12] Radboud Univ Nijmegen, Nijmegen Ctr Mol Life Sci, NL-6525 ED Nijmegen, Netherlands

[13] Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, NL-6525 ED Nijmegen, Netherlands

来源：

NATURE GENETICS | 2008年 / 40卷 / 11期

关键词：

D O I：

10.1038/ng.245

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Many proteins necessary for sound transduction have been identified through positional cloning of genes that cause deafness(1-3). We report here that mutations of LRTOMT are associated with profound nonsyndromic hearing loss at the DFNB63 locus on human chromosome 11q13.3-q13.4. LRTOMT has two alternative reading frames and encodes two different proteins, LRTOMT1 and LRTOMT2, detected by protein blot analyses. LRTOMT2 is a putative methyltransferase. During evolution, new transcripts can arise through partial or complete coalescence of genes(4). We provide evidence that in the primate lineage LRTOMT evolved from the fusion of two neighboring ancestral genes, which exist as separate genes (Lrrc51 and Tomt) in rodents.

引用

页码：1335 / 1340

页数：6

共 30 条

[1] PCDH15 is expressed in the neurosensory epithelium of the eye and ear and mutant alleles are responsible for both USH1F and DFNB23 [J].

Ahmed, ZM ;

Riazuddin, S ;

Ahmad, J ;

Bernstein, SL ;

Guo, Y ;

Sabar, MF ;

Sieving, P ;

Riazuddin, S ;

Griffith, AJ ;

Friedman, TB ;

Belyantseva, IA ;

Wilcox, ER .

HUMAN MOLECULAR GENETICS, 2003, 12 (24) :3215-3223

[2] Mutations of the protocadherin gene PCDH15 cause Usher syndrome type 1F [J].

Ahmed, ZM ;

Riazuddin, S ;

Bernstein, SL ;

Ahmed, Z ;

Khan, S ;

Griffith, AJ ;

Morell, RJ ;

Friedman, TB ;

Riazuddin, S ;

Wilcox, ER .

AMERICAN JOURNAL OF HUMAN GENETICS, 2001, 69 (01) :25-34

[3] Transcription-mediated gene fusion in the human genome [J].

Akiva, P ;

Toporik, A ;

Edelheit, S ;

Peretz, Y ;

Diber, A ;

Shemesh, R ;

Novik, A ;

Sorek, R .

GENOME RESEARCH, 2006, 16 (01) :30-36

[4] Myosin-XVa is required for tip localization of whirlin and differential elongation of hair-cell stereocilia [J].

Belyantseva, IA ;

Boger, ET ;

Naz, S ;

Frolenkov, GI ;

Sellers, JR ;

Ahmed, ZM ;

Griffith, AJ ;

Friedman, TB .

NATURE CELL BIOLOGY, 2005, 7 (02) :148-U60

[5] Kinetics and crystal structure of catechol-O-methyltransferase complex with co-substrate and a novel inhibitor with potential therapeutic application [J].

Bonifácio, MJ ;

Archer, M ;

Rodrigues, ML ;

Matias, PM ;

Learmonth, DA ;

Carrondo, MA ;

Soares-da-Silva, P .

MOLECULAR PHARMACOLOGY, 2002, 62 (04) :795-805

[6] SUGGESTIONS FOR SAFE RESIDUE SUBSTITUTIONS IN SITE-DIRECTED MUTAGENESIS [J].

BORDO, D ;

ARGOS, P .

JOURNAL OF MOLECULAR BIOLOGY, 1991, 217 (04) :721-729

[7] A first look at ARFome: Dual-coding genes in mammalian Genomes [J].

Chung, Wen-Yu ;

Wadhawan, Samir ;

Szklarczyk, Radek ;

Pond, Sergei Kosakovsky ;

Nekrutenko, Anton .

PLOS COMPUTATIONAL BIOLOGY, 2007, 3 (05) :855-861

[8] Mutations of ESRRB encoding estrogen-related receptor beta cause autosomal-recessive nonsyndromic hearing impairment DFNB35 [J].

Collin, Rob W. J. ;

Kalay, Ersan ;

Tariq, Muhammad ;

Peters, Theo ;

van der Zwaag, Bert ;

Venselaar, Hanka ;

Oostrik, Jaap ;

Lee, Kwanghyuk ;

Ahmed, Zubair M. ;

Caylan, Refik ;

Li, Yun ;

Spierenburg, Henk A. ;

Eyupoglu, Erol ;

Heister, Angelien ;

Riazuddin, Saima ;

Bahat, Elif ;

Ansar, Muhammad ;

Arslan, Selcuk ;

Wollnik, Bernd ;

Brunner, Han G. ;

Cremers, Cor W. R. J. ;

Karaguzel, Ahmet ;

Ahmad, Wasim ;

Cremers, Frans P. M. ;

Vriend, Gert ;

Friedman, Thomas B. ;

Riazuddin, Sheikh ;

Leal, Suzanne M. ;

Kremer, Hannie .

AMERICAN JOURNAL OF HUMAN GENETICS, 2008, 82 (01) :125-138

[9] Prestin, a new type of motor protein [J].

Dallos, P ;

Fakler, B .

NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2002, 3 (02) :104-111

[10] Human nonsyndromic sensorineural deafness [J].

Friedman, TB ;

Griffith, AJ .

ANNUAL REVIEW OF GENOMICS AND HUMAN GENETICS, 2003, 4 :341-402

← 1 2 3 →