Recessive mutations in RTN4IP1 cause isolated and syndromic optic neuropathies

Angebault Claire, Guichet Pierre-Olivier, Talmat-Amar Yasmina, Charif Majida, Gerber Sylvie, Fares-Taie Lucas, Gueguen Naig, Halloy François, Moore David, Amati-Bonneau Patrizia, Manes Gael, Hebrard Maxime, Bocquet Béatrice, Quilès Mélanie, Piro-Megy Camille, et al.. 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

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Quartile : Outlier, Sujet : GENETICS & HEREDITY

Liste HCERES des revues (en SHS) : oui

Thème(s) HCERES des revues (en SHS) : Psychologie-éthologie-ergonomie

Résumé : 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 identi- fied 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 mecha- nism 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.

Mots-clés Agrovoc : névropathie, mutation, carte génétique, morphogénèse, mitochondrie

Mots-clés géographiques Agrovoc : France

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