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 XiaArti Pandya, Michael A. Patton, Juan I. Young, Jun Aruga, Andrew H. Crosby

Research output: Contribution to journalArticle

32 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2094-2102
Number of pages9
JournalJournal of Clinical Investigation
Volume123
Issue number5
DOIs
StatePublished - May 1 2013

ASJC Scopus subject areas

  • Medicine(all)

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    Tekin, M., Chioza, B. A., Matsumoto, Y., Diaz-Horta, O., Cross, H. E., Duman, D., Kokotas, H., Moore-Barton, H. L., Sakoori, K., Ota, M., Odaka, Y. S., Foster, J., Cengiz, F. B., Tokgoz-Yilmaz, S., Tekeli, O., Grigoriadou, M., Petersen, M. B., Sreekantan-Nair, A., Gurtz, K., ... Crosby, A. H. (2013). SLITRK6 mutations cause myopia and deafness in humans and mice. Journal of Clinical Investigation, 123(5), 2094-2102. https://doi.org/10.1172/JCI65853