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J Clin Invest. 2013 May;123(5):2094-102. doi: 10.1172/JCI65853. Epub 2013 Apr 1.

SLITRK6 mutations cause myopia and deafness in humans and mice.

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1
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 33136, USA. mtekin@med.miami.edu

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.

PMID:
23543054
PMCID:
PMC3635725
DOI:
10.1172/JCI65853
[Indexed for MEDLINE]
Free PMC Article
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