A Truncating Mutation in SERPINB6 Is Associated with Autosomal-Recessive Nonsyndromic Sensorineural Hearing Loss

Aslı Sırmacı; Seyra Erbek; Justin Price; Mingqian Huang; Duygu Duman; F. Başak Cengiz; Güney Bademci; Suna Tokgöz-Yılmaz; Burcu Hişmi; Hilal Özdağ; Banu Öztürk; Sevsen Kulaksızoğlu; Erkan Yıldırım; Haris Kokotas; Maria Grigoriadou; Michael B Petersen; Hashem Shahin; Moien Kanaan; Mary-Claire King; Zheng-Yi Chen; Susan H Blanton; Xue Z Liu; Stephan Zuchner; Nejat Akar; Mustafa Tekin

doi:10.1016/j.ajhg.2010.04.004

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A Truncating Mutation in SERPINB6 Is Associated with Autosomal-Recessive Nonsyndromic Sensorineural Hearing Loss

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A Truncating Mutation in SERPINB6 Is Associated with Autosomal-Recessive Nonsyndromic Sensorineural Hearing Loss

Aslı Sırmacı, Seyra Erbek, Justin Price, Mingqian Huang, Duygu Duman, F. Başak Cengiz, Güney Bademci, Suna Tokgöz-Yılmaz, Burcu Hişmi, Hilal Özdağ, …

American journal of human genetics, Vol.86(5), pp.797-804

2010-05-14

DOI: https://doi.org/10.1016/j.ajhg.2010.04.004

PMCID: PMC2869020

PMID: 20451170

Abstract

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More than 270 million people worldwide have hearing loss that affects normal communication. Although astonishing progress has been made in the identification of more than 50 genes for deafness during the past decade, the majority of deafness genes are yet to be identified. In this study, we mapped a previously unknown autosomal-recessive nonsyndromic sensorineural hearing loss locus (DFNB91) to chromosome 6p25 in a consanguineous Turkish family. The degree of hearing loss was moderate to severe in affected individuals. We subsequently identified a nonsense mutation (p.E245X) in SERPINB6 , which is located within the linkage interval for DFNB91 and encodes for an intracellular protease inhibitor. The p.E245X mutation cosegregated in the family as a completely penetrant autosomal-recessive trait and was absent in 300 Turkish controls. The mRNA expression of SERPINB6 was reduced and production of protein was absent in the peripheral leukocytes of homozygotes, suggesting that the hearing loss is due to loss of function of SERPINB6. We also demonstrated that SERPINB6 was expressed primarily in the inner ear hair cells. We propose that SERPINB6 plays an important role in the inner ear in the protection against leakage of lysosomal content during stress and that loss of this protection results in cell death and 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: A Truncating Mutation in SERPINB6 Is Associated with Autosomal-Recessive Nonsyndromic Sensorineural Hearing Loss
Creators: Aslı Sırmacı - Dr. John T. Macdonald Department of Human Genetics, University of Miami, Miller School of Medicine, Miami, FL 33136, USA
Seyra Erbek - Department of Otorhinolaryngology, Baskent University School of Medicine, Ankara 06490, Turkey
Justin Price - Dr. John T. Macdonald Department of Human Genetics, University of Miami, Miller School of Medicine, Miami, FL 33136, USA
Mingqian Huang - Eaton-Peabody Laboratory, Department of Otolaryngology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston 02114, USA
Duygu Duman - Division of Genetics, Department of Pediatrics, Ankara University School of Medicine, Ankara 06100, Turkey
F. Başak Cengiz - Division of Genetics, Department of Pediatrics, Ankara University School of Medicine, Ankara 06100, Turkey
Güney Bademci - Dr. John T. Macdonald Department of Human Genetics, University of Miami, Miller School of Medicine, Miami, FL 33136, USA
Suna Tokgöz-Yılmaz - Division of Genetics, Department of Pediatrics, Ankara University School of Medicine, Ankara 06100, Turkey
Burcu Hişmi - Division of Genetics, Department of Pediatrics, Ankara University School of Medicine, Ankara 06100, Turkey
Hilal Özdağ - Biotechnology Institute, Ankara University, Ankara 06100, Turkey
Banu Öztürk - Department of Ophthalmology, Selcuk University Meram School of Medicine, Konya 42080, Turkey
Sevsen Kulaksızoğlu - Department of Biochemistry, Baskent University School of Medicine, Konya 42080, Turkey
Erkan Yıldırım - Department of Radiodiagnostics, Baskent University School of Medicine, Konya 42080, Turkey
Haris Kokotas - Department of Genetics, Institute of Child Health, ‘Aghia Sophia’ Children's Hospital, Athens 11527, Greece
Maria Grigoriadou - Department of Genetics, Institute of Child Health, ‘Aghia Sophia’ Children's Hospital, Athens 11527, Greece
Michael B Petersen - Department of Genetics, Institute of Child Health, ‘Aghia Sophia’ Children's Hospital, Athens 11527, Greece
Hashem Shahin - Department of Life Sciences, Bethlehem University, Bethlehem, Palestinian Authority
Moien Kanaan - Department of Life Sciences, Bethlehem University, Bethlehem, Palestinian Authority
Mary-Claire King - Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA 98195, USA
Zheng-Yi Chen - Eaton-Peabody Laboratory, Department of Otolaryngology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston 02114, USA
Susan H Blanton - Dr. John T. Macdonald Department of Human Genetics, University of Miami, Miller School of Medicine, Miami, FL 33136, USA
Xue Z Liu - John P. Hussman Institute for Human Genomics, University of Miami, Miller School of Medicine, Miami, FL 33136, USA
Stephan Zuchner - Dr. John T. Macdonald Department of Human Genetics, University of Miami, Miller School of Medicine, Miami, FL 33136, USA
Nejat Akar - Division of Genetics, Department of Pediatrics, Ankara University School of Medicine, Ankara 06100, Turkey
Mustafa Tekin - Dr. John T. Macdonald Department of Human Genetics, University of Miami, Miller School of Medicine, Miami, FL 33136, USA
Publication Details: American journal of human genetics, Vol.86(5), pp.797-804
Publisher: Elsevier
Academic Unit: Leadership Department; Miller School of Medicine; 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)
Language: English
Resource Type: Journal article
PMID: 20451170
PMCID: PMC2869020
Record Identifier: 991031560895402976