Letter abstract
Nature Genetics 40, 1335 - 1340 (2008)
Published online: 26 October 2008 | doi:10.1038/ng.245
Mutations of LRTOMT, a fusion gene with alternative reading frames, cause nonsyndromic deafness in humans
Zubair M Ahmed1,13, Saber Masmoudi2,13, Ersan Kalay3,4,5,13, Inna A Belyantseva1, Mohamed Ali Mosrati2, Rob W J Collin3,4, Saima Riazuddin1, Mounira Hmani-Aifa2, Hanka Venselaar6, Mayya N Kawar1, Abdelaziz Tlili2, Bert van der Zwaag7, Shahid Y Khan8, Leila Ayadi2, S Amer Riazuddin8, Robert J Morell1, Andrew J Griffith9, Ilhem Charfedine10, Refik Çaylan11, Jaap Oostrik4, Ahmet Karaguzel5, Abdelmonem Ghorbel10, Sheikh Riazuddin8, Thomas B Friedman1, Hammadi Ayadi2 & Hannie Kremer4,12
Many proteins necessary for sound transduction have been identified through positional cloning of genes that cause deafness1, 2, 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 genes4. 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.
- Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, Rockville, Maryland 20850, USA.
- Unité Cibles pour le Diagnostic et la Thérapie, Centre de Biotechnologie de Sfax, 3018 Tunisie.
- Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen 6500 HB, The Netherlands.
- Department of Otorhinolaryngology, Radboud University Nijmegen Medical Centre, Nijmegen 6500 HB, The Netherlands.
- Department of Medical Biology, Faculty of Medicine, Karadeniz Technical University, Trabzon 61080, Turkey.
- Center for Molecular and Biomolecular Informatics, Radboud University Nijmegen, Nijmegen 6500 HB, The Netherlands.
- Department of Neuroscience and Pharmacology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht 3584 CG, The Netherlands.
- National Center of Excellence in Molecular Biology, University of the Punjab, Lahore 53700, Pakistan.
- Otolaryngology Branch, National Institute on Deafness and Other Communication Disorders, Rockville, Maryland 20850, USA.
- Service d'O.R.L, C.H.U. Habib Bourguiba de Sfax, 3029 Tunisie.
- Department of Otorhinolaryngology, Faculty of Medicine, Karadeniz Technical University, Trabzon 61080, Turkey.
- Nijmegen Centre for Molecular Life Sciences and Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen, Nijmegen, The Netherlands.
- These authors contributed equally to this work.
Correspondence to: Hannie Kremer4,12 e-mail: H.Kremer@antrg.umcn.nl
Correspondence to: Hammadi Ayadi2 e-mail: directeur.general@cbs.rnrt.tn
Correspondence to: Thomas B Friedman1 e-mail: friedman@nidcd.nih.gov
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