Mutations in OTOGL, Encoding the Inner Ear Protein Otogelin-like, Cause Moderate Sensorineural Hearing Loss

Kemal O Yariz; Duygu Duman; Celia Zazo Seco; Julia Dallman; Mingqian Huang; Theo A Peters; Asli Sirmaci; Na Lu; Margit Schraders; Isaac Skromne; Jaap Oostrik; Oscar Diaz-Horta; Juan I Young; Suna Tokgoz-Yilmaz; Ozlem Konukseven; Hashem Shahin; Lisette Hetterschijt; Moien Kanaan; Anne M.M Oonk; Yvonne J.K Edwards; Huawei Li; Semra Atalay; Susan Blanton; Alexandra A DeSmidt; Xue-Zhong Liu; Ronald J.E Pennings; Zhongmin Lu; Zheng-Yi Chen; Hannie Kremer; Mustafa Tekin

doi:10.1016/j.ajhg.2012.09.011

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Mutations in OTOGL, Encoding the Inner Ear Protein Otogelin-like, Cause Moderate Sensorineural Hearing Loss

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Mutations in OTOGL, Encoding the Inner Ear Protein Otogelin-like, Cause Moderate Sensorineural Hearing Loss

Kemal O Yariz, Duygu Duman, Celia Zazo Seco, Julia Dallman, Mingqian Huang, Theo A Peters, Asli Sirmaci, Na Lu, Margit Schraders, Isaac Skromne, …

American journal of human genetics, Vol.91(5), pp.872-882

2012-11-02

DOI: https://doi.org/10.1016/j.ajhg.2012.09.011

PMCID: PMC3487139

PMID: 23122586

Abstract

Hereditary hearing loss is characterized by a high degree of genetic heterogeneity. Here we present OTOGL mutations, a homozygous one base pair deletion (c.1430 delT) causing a frameshift (p.Val477Glufs ∗ 25) in a large consanguineous family and two compound heterozygous mutations, c.547C>T (p.Arg183 ∗ ) and c.5238+5G>A, in a nonconsanguineous family with moderate nonsyndromic sensorineural hearing loss. OTOGL maps to the DFNB84 locus at 12q21.31 and encodes otogelin-like, which has structural similarities to the epithelial-secreted mucin protein family. We demonstrate that Otogl is expressed in the inner ear of vertebrates with a transcription level that is high in embryonic, lower in neonatal, and much lower in adult stages. Otogelin-like is localized to the acellular membranes of the cochlea and the vestibular system and to a variety of inner ear cells located underneath these membranes. Knocking down of otogl with morpholinos in zebrafish leads to sensorineural hearing loss and anatomical changes in the inner ear, supporting that otogelin-like is essential for normal inner ear function. We propose that OTOGL mutations affect the production and/or function of acellular structures of the inner ear, which ultimately leads to sensorineural hearing loss.

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Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.150 Hearing Loss; 1.150.421 Cochlea
Web Of Science research areas: Genetics & Heredity
ESI research areas: Molecular Biology & Genetics

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Title: Mutations in OTOGL, Encoding the Inner Ear Protein Otogelin-like, Cause Moderate Sensorineural Hearing Loss
Creators: Kemal O Yariz - John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL 33136, USA
Duygu Duman - Division of Pediatric Genetics, Ankara University School of Medicine, 06100 Ankara, Turkey
Celia Zazo Seco - Department of Otorhinolaryngology, Radboud University Nijmegen Medical Centre, 6500 HB Nijmegen, The Netherlands
Julia Dallman - Department of Biology, University of Miami, Miami, FL 33146, USA
Mingqian Huang - Eaton-Peabody Laboratory, Department of Otology and Laryngology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA 02114, USA
Theo A Peters - Department of Otorhinolaryngology, Radboud University Nijmegen Medical Centre, 6500 HB Nijmegen, The Netherlands
Asli Sirmaci - John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL 33136, USA
Na Lu - Eaton-Peabody Laboratory, Department of Otology and Laryngology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA 02114, USA
Margit Schraders - Department of Otorhinolaryngology, Radboud University Nijmegen Medical Centre, 6500 HB Nijmegen, The Netherlands
Isaac Skromne - Department of Biology, University of Miami, Miami, FL 33146, USA
Jaap Oostrik - Department of Otorhinolaryngology, Radboud University Nijmegen Medical Centre, 6500 HB Nijmegen, The Netherlands
Oscar Diaz-Horta - John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL 33136, USA
Juan I Young - John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL 33136, USA
Suna Tokgoz-Yilmaz - Division of Pediatric Genetics, Ankara University School of Medicine, 06100 Ankara, Turkey
Ozlem Konukseven - Hearing and Balance Disorders Diagnosis and Rehabilitation Center, Ataturk Research and Training Hospital, 06800 Ankara, Turkey
Hashem Shahin - Department of Life Sciences, Bethlehem University, Bethlehem, Palestine
Lisette Hetterschijt - Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, 6500 HB Nijmegen, The Netherlands
Moien Kanaan - Department of Life Sciences, Bethlehem University, Bethlehem, Palestine
Anne M.M Oonk - Department of Otorhinolaryngology, Radboud University Nijmegen Medical Centre, 6500 HB Nijmegen, The Netherlands
Yvonne J.K Edwards - John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL 33136, USA
Huawei Li - Department of Otology & Skull Base Surgery, Affiliated Eye and ENT Hospital of Fudan University, 83 Fenyang Road, Shanghai, 200031 China
Semra Atalay - Division of Pediatric Genetics, Ankara University School of Medicine, 06100 Ankara, Turkey
Susan Blanton - John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL 33136, USA
Alexandra A DeSmidt - Department of Biology, University of Miami, Miami, FL 33146, USA
Xue-Zhong Liu - John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL 33136, USA
Ronald J.E Pennings - Department of Otorhinolaryngology, Radboud University Nijmegen Medical Centre, 6500 HB Nijmegen, The Netherlands
Zhongmin Lu - Department of Biology, University of Miami, Miami, FL 33146, USA
Zheng-Yi Chen - Eaton-Peabody Laboratory, Department of Otology and Laryngology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA 02114, USA
Hannie Kremer - Department of Otorhinolaryngology, Radboud University Nijmegen Medical Centre, 6500 HB Nijmegen, The Netherlands
Mustafa Tekin - John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL 33136, USA
Publication Details: American journal of human genetics, Vol.91(5), pp.872-882
Publisher: Elsevier
Academic Unit: Miller School of Medicine; College of A&S; John P. Hussman Institute for Human Genomics; UMMG Department of Otolaryngology; UMMG Dept of Human Genetics - Clinical and Translational Genetics; UMMG Dept of Human Genetics (Dr. John T. Macdonald Foundation); A&S - Biology
Language: English
Resource Type: Journal article
PMID: 23122586
PMCID: PMC3487139
Record Identifier: 991031560070302976