SLITRK6 mutations cause myopia and deafness in humans and mice

Mustafa Tekin; Barry A Chioza; Yoshifumi Matsumoto; Oscar Diaz-Horta; Harold E Cross; Duygu Duman; Haris Kokotas; Heather L Moore-Barton; Kazuto Sakoori; Maya Ota; Yuri S Odaka; Joseph Foster; F. Basak Cengiz; Suna Tokgoz-Yilmaz; Oya Tekeli; Maria Grigoriadou; Michael B Petersen; Ajith Sreekantan-Nair; Kay Gurtz; Xia-Juan Xia; Arti Pandya; Michael A Patton; Juan I Young; Jun Aruga; Andrew H Crosby

doi:10.1172/JCI65853

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SLITRK6 mutations cause myopia and deafness in humans and mice

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SLITRK6 mutations cause myopia and deafness in humans and mice

Mustafa Tekin, Barry A Chioza, Yoshifumi Matsumoto, Oscar Diaz-Horta, Harold E Cross, Duygu Duman, Haris Kokotas, Heather L Moore-Barton, Kazuto Sakoori, Maya Ota, …

The Journal of clinical investigation, Vol.123(5), pp.2094-2102

2013-05-01

DOI: https://doi.org/10.1172/JCI65853

PMCID: PMC3635725

PMID: 23543054

Abstract

Myopia is by far the most common human eye disorder that is known to have a clear, albeit poorly defined, heritable component. In this study, we describe an autosomal-recessive syndrome characterized by high myopia and sensorineural deafness. Our molecular investigation in 3 families led to the identification of 3 homozygous nonsense mutations (p.R181X, p.S297X, and p.Q414X) in SLIT and NTRK-like family, member 6 ( SLITRK6 ), a leucine-rich repeat domain transmembrane protein. All 3 mutant SLITRK6 proteins displayed defective cell surface localization. High-resolution MRI of WT and Slitrk6 -deficient mouse eyes revealed axial length increase in the mutant (the endophenotype of myopia). Additionally, mutant mice exhibited auditory function deficits that mirrored the human phenotype. Histological investigation of WT and Slitrk6 -deficient mouse retinas in postnatal development indicated a delay in synaptogenesis in Slitrk6 -deficient animals. Taken together, our results showed that SLITRK6 plays a crucial role in the development of normal hearing as well as vision in humans and in mice and that its disruption leads to a syndrome characterized by severe myopia and deafness.

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Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.36 Ophthalmology; 1.36.813 Myopia
Web Of Science research areas: Medicine, Research & Experimental
ESI research areas: Clinical Medicine

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Title: SLITRK6 mutations cause myopia and deafness in humans and mice
Creators: Mustafa Tekin - John P. Hussman Institute for Human Genomics and Dr. John T. Macdonald Department of Human Genetics, University of Miami Miller School of Medicine, Miami, Florida, USA
Barry A Chioza - John P. Hussman Institute for Human Genomics and Dr. John T. Macdonald Department of Human Genetics, University of Miami Miller School of Medicine, Miami, Florida, USA
Yoshifumi Matsumoto - John P. Hussman Institute for Human Genomics and Dr. John T. Macdonald Department of Human Genetics, University of Miami Miller School of Medicine, Miami, Florida, USA
Oscar Diaz-Horta - John P. Hussman Institute for Human Genomics and Dr. John T. Macdonald Department of Human Genetics, University of Miami Miller School of Medicine, Miami, Florida, USA
Harold E Cross - John P. Hussman Institute for Human Genomics and Dr. John T. Macdonald Department of Human Genetics, University of Miami Miller School of Medicine, Miami, Florida, USA
Duygu Duman - John P. Hussman Institute for Human Genomics and Dr. John T. Macdonald Department of Human Genetics, University of Miami Miller School of Medicine, Miami, Florida, USA
Haris Kokotas - John P. Hussman Institute for Human Genomics and Dr. John T. Macdonald Department of Human Genetics, University of Miami Miller School of Medicine, Miami, Florida, USA
Heather L Moore-Barton - John P. Hussman Institute for Human Genomics and Dr. John T. Macdonald Department of Human Genetics, University of Miami Miller School of Medicine, Miami, Florida, USA
Kazuto Sakoori - John P. Hussman Institute for Human Genomics and Dr. John T. Macdonald Department of Human Genetics, University of Miami Miller School of Medicine, Miami, Florida, USA
Maya Ota - John P. Hussman Institute for Human Genomics and Dr. John T. Macdonald Department of Human Genetics, University of Miami Miller School of Medicine, Miami, Florida, USA
Yuri S Odaka - John P. Hussman Institute for Human Genomics and Dr. John T. Macdonald Department of Human Genetics, University of Miami Miller School of Medicine, Miami, Florida, USA
Joseph Foster - John P. Hussman Institute for Human Genomics and Dr. John T. Macdonald Department of Human Genetics, University of Miami Miller School of Medicine, Miami, Florida, USA
F. Basak Cengiz - John P. Hussman Institute for Human Genomics and Dr. John T. Macdonald Department of Human Genetics, University of Miami Miller School of Medicine, Miami, Florida, USA
Suna Tokgoz-Yilmaz - John P. Hussman Institute for Human Genomics and Dr. John T. Macdonald Department of Human Genetics, University of Miami Miller School of Medicine, Miami, Florida, USA
Oya Tekeli - John P. Hussman Institute for Human Genomics and Dr. John T. Macdonald Department of Human Genetics, University of Miami Miller School of Medicine, Miami, Florida, USA
Maria Grigoriadou - John P. Hussman Institute for Human Genomics and Dr. John T. Macdonald Department of Human Genetics, University of Miami Miller School of Medicine, Miami, Florida, USA
Michael B Petersen - John P. Hussman Institute for Human Genomics and Dr. John T. Macdonald Department of Human Genetics, University of Miami Miller School of Medicine, Miami, Florida, USA
Ajith Sreekantan-Nair - John P. Hussman Institute for Human Genomics and Dr. John T. Macdonald Department of Human Genetics, University of Miami Miller School of Medicine, Miami, Florida, USA
Kay Gurtz - John P. Hussman Institute for Human Genomics and Dr. John T. Macdonald Department of Human Genetics, University of Miami Miller School of Medicine, Miami, Florida, USA
Xia-Juan Xia - John P. Hussman Institute for Human Genomics and Dr. John T. Macdonald Department of Human Genetics, University of Miami Miller School of Medicine, Miami, Florida, USA
Arti Pandya - John P. Hussman Institute for Human Genomics and Dr. John T. Macdonald Department of Human Genetics, University of Miami Miller School of Medicine, Miami, Florida, USA
Michael A Patton - John P. Hussman Institute for Human Genomics and Dr. John T. Macdonald Department of Human Genetics, University of Miami Miller School of Medicine, Miami, Florida, USA
Juan I Young - John P. Hussman Institute for Human Genomics and Dr. John T. Macdonald Department of Human Genetics, University of Miami Miller School of Medicine, Miami, Florida, USA
Jun Aruga - John P. Hussman Institute for Human Genomics and Dr. John T. Macdonald Department of Human Genetics, University of Miami Miller School of Medicine, Miami, Florida, USA
Andrew H Crosby - John P. Hussman Institute for Human Genomics and Dr. John T. Macdonald Department of Human Genetics, University of Miami Miller School of Medicine, Miami, Florida, USA
Publication Details: The Journal of clinical investigation, Vol.123(5), pp.2094-2102
Publisher: American Society for Clinical Investigation
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)
Language: English
Resource Type: Journal article
PMID: 23543054
PMCID: PMC3635725
Record Identifier: 991031559244402976