Journalartikel
Autorenliste: Angebault, Claire; Guichet, Pierre-Olivier; Talmat-Amar, Yasmina; Charif, Majida; Gerber, Sylvie; Fares-Taie, Lucas; Gueguen, Naig; Halloyn, Francois; Moore, David; Amati-Bonneau, Patrizia; Manes, Gael; Hebrard, Maxime; Bocquet, Beatrice; Quiles, Melanie; Piro-Megy, Camille; Teigell, Marisa; Delettre, Cecile; Rossel, Mireille; Meunier, Isabelle; Preising, Markus; Lorenz, Birgit; Carelli, Valerio; Chinnery, Patrick F.; Yu-Wai-Man, Patrick; Kaplan, Josseline; Roubertie, Agathe; Barakat, Abdelhamid; Bonneau, Dominique; Reynier, Pascal; Rozet, Jean-Michel; Bomont, Pascale; Hamel, Christian P.; Lenaers, Guy
Jahr der Veröffentlichung: 2015
Seiten: 754-760
Zeitschrift: American Journal of Human Genetics
Bandnummer: 97
Heftnummer: 5
ISSN: 0002-9297
eISSN: 1537-6605
Open Access Status: Green
DOI Link: https://doi.org/10.1016/j.ajhg.2015.09.012
Verlag: Cell Press
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.
Zitierstile
Harvard-Zitierstil: Angebault, C., Guichet, P., Talmat-Amar, Y., Charif, M., Gerber, S., Fares-Taie, L., et al. (2015) Recessive Mutations in RTN4IP1 Cause Isolated and Syndromic Optic Neuropathies, American Journal of Human Genetics, 97(5), pp. 754-760. https://doi.org/10.1016/j.ajhg.2015.09.012
APA-Zitierstil: Angebault, C., Guichet, P., Talmat-Amar, Y., Charif, M., Gerber, S., Fares-Taie, L., Gueguen, N., Halloyn, F., Moore, D., Amati-Bonneau, P., Manes, G., Hebrard, M., Bocquet, B., Quiles, M., Piro-Megy, C., Teigell, M., Delettre, C., Rossel, M., Meunier, I., ...Lenaers, G. (2015). Recessive Mutations in RTN4IP1 Cause Isolated and Syndromic Optic Neuropathies. American Journal of Human Genetics. 97(5), 754-760. https://doi.org/10.1016/j.ajhg.2015.09.012
Schlagwörter
ATROPHY; MITOCHONDRIAL PROTEIN; NOGO; OPA1
