MPZL2 is a novel gene associated with autosomal recessive nonsyndromic moderate hearing loss

Guney Bademci; Clemer Abad; Armagan Incesulu; Abolfazl Rad; Ozgul Alper; Susanne M Kolb; Filiz B Cengiz; Oscar Diaz-Horta; Fatma Silan; Ercan Mihci; Emre Ocak; Maryam Najafi; Reza Maroofian; Elanur Yilmaz; Banu G Nur; Duygu Duman; Shengru Guo; David W Sant; Gaofeng Wang; Paula V Monje; Thomas Haaf; Susan H Blanton; Barbara Vona; Katherina Walz; Mustafa Tekin

doi:10.1007/s00439-018-1901-4

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MPZL2 is a novel gene associated with autosomal recessive nonsyndromic moderate hearing loss

Journal article

Open access

Peer reviewed

MPZL2 is a novel gene associated with autosomal recessive nonsyndromic moderate hearing loss

Guney Bademci, Clemer Abad, Armagan Incesulu, Abolfazl Rad, Ozgul Alper, Susanne M Kolb, Filiz B Cengiz, Oscar Diaz-Horta, Fatma Silan, Ercan Mihci, …

Human genetics, Vol.137(6-7), pp.479-486

2018-07

DOI: https://doi.org/10.1007/s00439-018-1901-4

PMCID: PMC6478175

PMID: 29982980

Abstract

Cell Adhesion Molecules - genetics

Deafness - genetics

Gene Frequency

Humans

Deafness - physiopathology

Male

Schwann Cells - pathology

Hearing Loss, Sensorineural - genetics

Ear, Inner - physiopathology

Genes, Recessive

Jews - genetics

Hair Cells, Auditory, Inner - pathology

Haplotypes - genetics

Animals

Turkey

Hair Cells, Auditory, Inner - metabolism

Pedigree

Female

Mice

Mutation

Iran - epidemiology

Ear, Inner - growth & development

Hearing Loss, Sensorineural - physiopathology

While recent studies have revealed a substantial portion of the genes underlying human hearing loss, the extensive genetic landscape has not been completely explored. Here, we report a loss-of-function variant (c.72delA) in MPZL2 in three unrelated multiplex families from Turkey and Iran with autosomal recessive nonsyndromic hearing loss. The variant co-segregates with moderate sensorineural hearing loss in all three families. We show a shared haplotype flanking the variant in our families implicating a single founder. While rare in other populations, the allele frequency of the variant is ~ 0.004 in Ashkenazi Jews, suggesting that it may be an important cause of moderate hearing loss in that population. We show that Mpzl2 is expressed in mouse inner ear, and the protein localizes in the auditory inner and outer hair cells, with an asymmetric subcellular localization. We thus present MPZL2 as a novel gene associated with 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: MPZL2 is a novel gene associated with autosomal recessive nonsyndromic moderate hearing loss
Creators: Guney Bademci - John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, 1501 NW 10th Avenue, BRB-610 (M-860), Miami, FL, 33136, USA
Clemer Abad - John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, 1501 NW 10th Avenue, BRB-610 (M-860), Miami, FL, 33136, USA
Armagan Incesulu - Department of Otorhinolaryngology, Faculty of Medicine, Eskisehir Osmangazi University, 26040, Eskisehir, Turkey
Abolfazl Rad - Cellular and Molecular Research Center, Sabzevar University of Medical Sciences, Sabzevar, 009851, Iran
Ozgul Alper - Department of Medical Biology and Genetics, Faculty of Medicine, Akdeniz University, 07070, Antalya, Turkey
Susanne M Kolb - Institute of Human Genetics, Julius Maximilians University Würzburg, 97074, Würzburg, Germany
Filiz B Cengiz - John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, 1501 NW 10th Avenue, BRB-610 (M-860), Miami, FL, 33136, USA
Oscar Diaz-Horta - John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, 1501 NW 10th Avenue, BRB-610 (M-860), Miami, FL, 33136, USA
Fatma Silan - Department of Medical Genetics, Canakkale Onsekiz Mart University School of Medicine, 17100, Canakkale, Turkey
Ercan Mihci - Department of Pediatric Genetics, Akdeniz University School of Medicine, 07070, Antalya, Turkey
Emre Ocak - Department of Otolaryngology, Ankara University School of Medicine, 06260, Ankara, Turkey
Maryam Najafi - Genome Research Division, Human Genetics Department, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525 KL, Nijmegen, The Netherlands
Reza Maroofian - Genetics and Molecular Cell Sciences Research Centre, St George's, University of London, Cranmer Terrace, London, SW17 0RE, UK
Elanur Yilmaz - Department of Medical Biology and Genetics, Faculty of Medicine, Akdeniz University, 07070, Antalya, Turkey
Banu G Nur - Department of Pediatric Genetics, Akdeniz University School of Medicine, 07070, Antalya, Turkey
Duygu Duman - Division of Genetics, Department of Pediatrics, Ankara University School of Medicine, 06260, Ankara, Turkey
Shengru Guo - John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, 1501 NW 10th Avenue, BRB-610 (M-860), Miami, FL, 33136, USA
David W Sant - John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, 1501 NW 10th Avenue, BRB-610 (M-860), Miami, FL, 33136, USA
Gaofeng Wang - Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, 33136, USA
Paula V Monje - The Miami Project to Cure Paralysis and the Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, FL, 33136, USA
Thomas Haaf - Institute of Human Genetics, Julius Maximilians University Würzburg, 97074, Würzburg, Germany
Susan H Blanton - Dr. John T. Macdonald Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL, 33136, USA
Barbara Vona - Department of Otorhinolaryngology, Head and Neck Surgery, Tübingen Hearing Research Centre (THRC), Eberhard Karls University Tübingen, 72076, Tübingen, Germany
Katherina Walz - Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, FL, 33136, USA
Mustafa Tekin - Dr. John T. Macdonald Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL, 33136, USA. mtekin@miami.edu
Publication Details: Human genetics, Vol.137(6-7), pp.479-486
Publisher: Germany
Grant note: T32 EY023194 / NEI NIH HHS R01DC09645 / NIDCD NIH HHS R01 DC012836 / NIDCD NIH HHS R01DC012836 / NIDCD NIH HHS R01 DC009645 / NIDCD NIH HHS
Academic Unit: Miller School of Medicine; John P. Hussman Institute for Human Genomics; UMMG Dept of Human Genetics - Clinical and Translational Genetics; UMMG Dept of Human Genetics (Dr. John T. Macdonald Foundation); UMMG Dept of Neurological Surgery
Language: English
Resource Type: Journal article
PMID: 29982980
PMCID: PMC6478175
Record Identifier: 991031577178002976