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

Zubair M. Ahmed; Saber Masmoudi; Ersan Kalay; Inna A. Belyantseva; Mohamed Ali Mosrati; Rob W.J. Collin; Saima Riazuddin; Mounira Hmani-Aifa; Hanka Venselaar; Mayya N. Kawar; Abdelaziz Tlili; Bert van der Zwaag; Shahid Y. Khan; Leila Ayadi; S. Amer Riazuddin; Robert J. Morell; Andrew J. Griffith; Ilhem Charfedine; Refik Ҫaylan; Jaap Oostrik; Ahmet Karaguzel; Abdelmonem Ghorbel; Sheikh Riazuddin; Thomas B. Friedman; Hammadi Ayadi; Hannie Kremer

doi:10.1038/ng.245

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

Zubair M. Ahmed, Saber Masmoudi, Ersan Kalay, Inna A. Belyantseva, Mohamed Ali Mosrati, Rob W.J. Collin, Saima Riazuddin, Mounira Hmani-Aifa, Hanka Venselaar, Mayya N. Kawar, Abdelaziz Tlili, Bert van der Zwaag, Shahid Y. Khan, Leila Ayadi, S. Amer Riazuddin, Robert J. Morell, Andrew J. Griffith, Ilhem Charfedine, Refik Ҫaylan, Jaap OostrikAhmet Karaguzel, Abdelmonem Ghorbel, Sheikh Riazuddin, Thomas B. Friedman, Hammadi Ayadi, Hannie Kremer

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Abstract

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 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.

Original language	English (US)
Pages (from-to)	1335-1340
Number of pages	6
Journal	Nature genetics
Volume	40
Issue number	11
DOIs	https://doi.org/10.1038/ng.245
State	Published - Nov 2008
Externally published	Yes

ASJC Scopus subject areas

Genetics

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Ahmed, Z. M., Masmoudi, S., Kalay, E., Belyantseva, I. A., Mosrati, M. A., Collin, R. W. J., Riazuddin, S., Hmani-Aifa, M., Venselaar, H., Kawar, M. N., Tlili, A., van der Zwaag, B., Khan, S. Y., Ayadi, L., Riazuddin, S. A., Morell, R. J., Griffith, A. J., Charfedine, I., Ҫaylan, R., ... Kremer, H. (2008). Mutations of LRTOMT, a fusion gene with alternative reading frames, cause nonsyndromic deafness in humans. Nature genetics, 40(11), 1335-1340. https://doi.org/10.1038/ng.245

Ahmed, ZM, Masmoudi, S, Kalay, E, Belyantseva, IA, Mosrati, MA, Collin, RWJ, Riazuddin, S, Hmani-Aifa, M, Venselaar, H, Kawar, MN, Tlili, A, van der Zwaag, B, Khan, SY, Ayadi, L, Riazuddin, SA, Morell, RJ, Griffith, AJ, Charfedine, I, Ҫaylan, R, Oostrik, J, Karaguzel, A, Ghorbel, A, Riazuddin, S, Friedman, TB, Ayadi, H & Kremer, H 2008, 'Mutations of LRTOMT, a fusion gene with alternative reading frames, cause nonsyndromic deafness in humans', Nature genetics, vol. 40, no. 11, pp. 1335-1340. https://doi.org/10.1038/ng.245

@article{054a706c81a440c6b4be7604d7ca48a6,

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

abstract = "Many proteins necessary for sound transduction have been identified through positional cloning of genes that cause deafness1-3. 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.",

author = "Ahmed, {Zubair M.} and Saber Masmoudi and Ersan Kalay and Belyantseva, {Inna A.} and Mosrati, {Mohamed Ali} and Collin, {Rob W.J.} and Saima Riazuddin and Mounira Hmani-Aifa and Hanka Venselaar and Kawar, {Mayya N.} and Abdelaziz Tlili and {van der Zwaag}, Bert and Khan, {Shahid Y.} and Leila Ayadi and Riazuddin, {S. Amer} and Morell, {Robert J.} and Griffith, {Andrew J.} and Ilhem Charfedine and Refik Ҫaylan and Jaap Oostrik and Ahmet Karaguzel and Abdelmonem Ghorbel and Sheikh Riazuddin and Friedman, {Thomas B.} and Hammadi Ayadi and Hannie Kremer",

note = "Funding Information: We thank the families for their participation in this study, which was supported by NIDCD/NIH (intramural research fund ZO1DC00035-06 and ZO1DC00035-06 to T.B.F., ZO1DC000060 and ZO1DC000064 to A.J.G.), funds from the European Commission FP6 Integrated Project EUROHEAR (contract number LSHG-CT-20054-512063:2), the Heinsius Houbolt Foundation and the Karadeniz Technical University Research Fund (contract numbers 2002.114.001.3 and 2006.114.001.1). In Tunisia work was also funded by Le Minist{\`e}re de l{\textquoteright}Enseignement Sup{\'e}rieur, de la Recherche Scientifique et de la Technologie, Tunisia. In Pakistan the Higher Education Commission and the Ministry of Science and Technology in Islamabad, Pakistan supported this project. We thank B. Ploplis, M. Ansari, A. Lagziel, E. Boger, S. Kitajiri, E. van Wijk, T. Peters and H. Spierenburg for their technical help and G. Vriend, F. Cremers, H. Brunner and C. Cremers for discussion. We also thank J. Bird, D. Drayna, M. Meisler and S. Sullivan for advice and comments in preparing the manuscript. We thank the Southwest National Primate Research Center, San Antonio, Texas for providing brain tissue samples from chimpanzee and baboon, and the Duke Lemur Center, Durham, North Carolina for brain tissue samples from a lemur.",

year = "2008",

month = nov,

doi = "10.1038/ng.245",

language = "English (US)",

volume = "40",

pages = "1335--1340",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "11",

}

TY - JOUR

T1 - Mutations of LRTOMT, a fusion gene with alternative reading frames, cause nonsyndromic deafness in humans

AU - Ahmed, Zubair M.

AU - Masmoudi, Saber

AU - Kalay, Ersan

AU - Belyantseva, Inna A.

AU - Mosrati, Mohamed Ali

AU - Collin, Rob W.J.

AU - Riazuddin, Saima

AU - Hmani-Aifa, Mounira

AU - Venselaar, Hanka

AU - Kawar, Mayya N.

AU - Tlili, Abdelaziz

AU - van der Zwaag, Bert

AU - Khan, Shahid Y.

AU - Ayadi, Leila

AU - Riazuddin, S. Amer

AU - Morell, Robert J.

AU - Griffith, Andrew J.

AU - Charfedine, Ilhem

AU - Ҫaylan, Refik

AU - Oostrik, Jaap

AU - Karaguzel, Ahmet

AU - Ghorbel, Abdelmonem

AU - Riazuddin, Sheikh

AU - Friedman, Thomas B.

AU - Ayadi, Hammadi

AU - Kremer, Hannie

N1 - Funding Information: We thank the families for their participation in this study, which was supported by NIDCD/NIH (intramural research fund ZO1DC00035-06 and ZO1DC00035-06 to T.B.F., ZO1DC000060 and ZO1DC000064 to A.J.G.), funds from the European Commission FP6 Integrated Project EUROHEAR (contract number LSHG-CT-20054-512063:2), the Heinsius Houbolt Foundation and the Karadeniz Technical University Research Fund (contract numbers 2002.114.001.3 and 2006.114.001.1). In Tunisia work was also funded by Le Ministère de l’Enseignement Supérieur, de la Recherche Scientifique et de la Technologie, Tunisia. In Pakistan the Higher Education Commission and the Ministry of Science and Technology in Islamabad, Pakistan supported this project. We thank B. Ploplis, M. Ansari, A. Lagziel, E. Boger, S. Kitajiri, E. van Wijk, T. Peters and H. Spierenburg for their technical help and G. Vriend, F. Cremers, H. Brunner and C. Cremers for discussion. We also thank J. Bird, D. Drayna, M. Meisler and S. Sullivan for advice and comments in preparing the manuscript. We thank the Southwest National Primate Research Center, San Antonio, Texas for providing brain tissue samples from chimpanzee and baboon, and the Duke Lemur Center, Durham, North Carolina for brain tissue samples from a lemur.

PY - 2008/11

Y1 - 2008/11

N2 - Many proteins necessary for sound transduction have been identified through positional cloning of genes that cause deafness1-3. 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.

AB - Many proteins necessary for sound transduction have been identified through positional cloning of genes that cause deafness1-3. 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.

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SN - 1061-4036

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JO - Nature Genetics

JF - Nature Genetics

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ER -

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

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