Published in
Cell Press, American Journal of Human Genetics, 5(97), p. 769, 2015
DOI: 10.1016/j.ajhg.2015.10.015
Cell Press, American Journal of Human Genetics, 5(97), p. 754-760, 2015
DOI: 10.1016/j.ajhg.2015.09.012
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- [www.ncbi.nlm.nih.gov] | PDF
- [www.researchgate.net]
- [www.ncbi.nlm.nih.gov] | PDF
- [europepmc.org] | PDF
- [europepmc.org] | PDF
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Recessive Mutations in RTN4IP1 Cause Isolated and Syndromic Optic Neuropathies
,
François Halloy ,
David Moore,
Patrizia Amati-Bonneau,
Gael Manes,
Béatrice Bocquet,
Mélanie Quiles,
Maxime Hebrard
and other authors.
Full text: Download
Abstract
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.