TY - JOUR
T1 - Recessive mutations in RTN4IP1 cause isolated and syndromic optic neuropathies
AU - Angebault, Claire
AU - Guichet, Pierre Olivier
AU - Talmat-Amar, Yasmina
AU - Charif, Majida
AU - Gerber, Sylvie
AU - Fares-Taie, Lucas
AU - Gueguen, Naig
AU - Halloy, François
AU - Moore, David
AU - Amati-Bonneau, Patrizia
AU - Manes, Gael
AU - Hebrard, Maxime
AU - Bocquet, Béatrice
AU - Quiles, Mélanie
AU - Piro-Mégy, Camille
AU - Teigell, Marisa
AU - Delettre, Cécile
AU - Rossel, Mireille
AU - Meunier, Isabelle
AU - Preising, Markus
AU - Lorenz, Birgit
AU - Carelli, Valerio
AU - Chinnery, Patrick F.
AU - Yu-Wai-Man, Patrick
AU - Kaplan, Josseline
AU - Roubertie, Agathe
AU - Barakat, Abdelhamid
AU - Bonneau, Dominique
AU - Reynier, Pascal
AU - Rozet, Jean Michel
AU - Bomont, Pascale
AU - Hamel, Christian P.
AU - Lenaers, Guy
PY - 2015/11/5
Y1 - 2015/11/5
N2 - 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.
AB - 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.
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U2 - 10.1016/j.ajhg.2015.09.012
DO - 10.1016/j.ajhg.2015.09.012
M3 - Article
AN - SCOPUS:84947924596
VL - 97
SP - 754
EP - 760
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
SN - 0002-9297
IS - 5
ER -