論文 - 詳細
| RRC ID | 69220 |
|---|---|
| 著者 | Tekin M, Chioza BA, Matsumoto Y, Diaz-Horta O, Cross HE, Duman D, Kokotas H, Moore-Barton HL, Sakoori K, Ota M, Odaka YS, Foster J 2nd, Cengiz FB, Tokgoz-Yilmaz S, Tekeli O, Grigoriadou M, Petersen MB, Sreekantan-Nair A, Gurtz K, Xia XJ, Pandya A, Patton MA, Young JI, Aruga J, Crosby AH. |
| タイトル | SLITRK6 mutations cause myopia and deafness in humans and mice. |
| ジャーナル | J Clin Invest |
| 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. |
| 巻・号 | 123(5) |
| ページ | 2094-102 |
| 公開日 | 2013-5-1 |
| DOI | 10.1172/JCI65853 |
| PII | 65853 |
| PMID | 23543054 |
| PMC | PMC3635725 |
| MeSH | Adolescent Adult Animals Child Codon, Nonsense Female Hearing Hearing Loss, Sensorineural / genetics* Humans Infant Male Membrane Proteins / genetics* Mice Mice, Knockout Middle Aged Mutation Myopia / genetics* Pedigree Phenotype Protein Structure, Tertiary Young Adult |
| IF | 11.864 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 15 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | PC-12(RCB0009) |