| First Author | Angebault C | Year | 2015 |
| Journal | Am J Hum Genet | Volume | 97 |
| Issue | 5 | Pages | 754-60 |
| PubMed ID | 26593267 | Mgi Jnum | J:233622 |
| Mgi Id | MGI:5787722 | Doi | 10.1016/j.ajhg.2015.09.012 |
| Citation | Angebault C, et al. (2015) Recessive Mutations in RTN4IP1 Cause Isolated and Syndromic Optic Neuropathies. Am J Hum Genet 97(5):754-60 |
| abstractText | Autosomal-recessive optic neuropathies are rare blinding conditions related to retinal ganglion cell (RGC) and optic-nerve degeneration, for which only mutations in TMEM126A and ACO2 are known. In four families with early-onset recessive optic neuropathy, we identified mutations in RTN4IP1, which encodes a mitochondrial ubiquinol oxydo-reductase. RTN4IP1 is a partner of RTN4 (also known as NOGO), and its ortholog Rad8 in C. elegans is involved in UV light response. Analysis of fibroblasts from affected individuals with a RTN4IP1 mutation showed loss of the altered protein, a deficit of mitochondrial respiratory complex I and IV activities, and increased susceptibility to UV light. Silencing of RTN4IP1 altered the number and morphogenesis of mouse RGC dendrites in vitro and the eye size, neuro-retinal development, and swimming behavior in zebrafish in vivo. Altogether, these data point to a pathophysiological mechanism responsible for RGC early degeneration and optic neuropathy and linking RTN4IP1 functions to mitochondrial physiology, response to UV light, and dendrite growth during eye maturation. |
