SLITRK6 mutations cause myopia and deafness in humans and mice


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Tekin M., Chioza B. A., Matsumoto Y., Diaz-Horta O., Cross H. E., Duman D., ...More

JOURNAL OF CLINICAL INVESTIGATION, vol.123, no.5, pp.2094-2102, 2013 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 123 Issue: 5
  • Publication Date: 2013
  • Doi Number: 10.1172/jci65853
  • Journal Name: JOURNAL OF CLINICAL INVESTIGATION
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.2094-2102
  • Hacettepe University Affiliated: No

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.