PUBLICATION
Recessive Mutations in RTN4IP1 Cause Isolated and Syndromic Optic Neuropathies
- Authors
- Angebault, C., Guichet, P.O., Talmat-Amar, Y., Charif, M., Gerber, S., Fares-Taie, L., Gueguen, N., Halloy, F., Moore, D., Amati-Bonneau, P., Manes, G., Hebrard, M., Bocquet, B., Quiles, M., Piro-Mégy, C., Teigell, M., Delettre, C., Rossel, M., Meunier, I., Preising, M., Lorenz, B., Carelli, V., Chinnery, P.F., Yu-Wai-Man, P., Kaplan, J., Roubertie, A., Barakat, A., Bonneau, D., Reynier, P., Rozet, J.M., Bomont, P., Hamel, C.P., Lenaers, G.
- ID
- ZDB-PUB-151125-14
- Date
- 2015
- Source
- American journal of human genetics 97: 754-60 (Journal)
- Registered Authors
- Bomont, Pascale, Rossel, Mireille
- Keywords
- none
- MeSH Terms
-
- Amino Acid Sequence
- Animals
- Carrier Proteins/antagonists & inhibitors
- Carrier Proteins/genetics*
- Carrier Proteins/metabolism
- Case-Control Studies
- Cells, Cultured
- Electron Transport Complex I
- Female
- Fibroblasts/metabolism
- Fibroblasts/pathology*
- Follow-Up Studies
- Genes, Recessive
- Humans
- Male
- Mice
- Mitochondria/genetics
- Mitochondria/pathology*
- Mitochondrial Proteins/antagonists & inhibitors
- Mitochondrial Proteins/genetics*
- Mitochondrial Proteins/metabolism
- Molecular Sequence Data
- Mutation/genetics*
- Nerve Degeneration
- Optic Nerve Diseases/genetics*
- Optic Nerve Diseases/pathology*
- Pedigree
- Prognosis
- Retinal Ganglion Cells/metabolism
- Retinal Ganglion Cells/pathology*
- Sequence Homology, Amino Acid
- Zebrafish/genetics
- Zebrafish/growth & development
- Zebrafish/metabolism
- PubMed
- 26593267 Full text @ Am. J. Hum. Genet.
Citation
Angebault, C., Guichet, P.O., Talmat-Amar, Y., Charif, M., Gerber, S., Fares-Taie, L., Gueguen, N., Halloy, F., Moore, D., Amati-Bonneau, P., Manes, G., Hebrard, M., Bocquet, B., Quiles, M., Piro-Mégy, C., Teigell, M., Delettre, C., Rossel, M., Meunier, I., Preising, M., Lorenz, B., Carelli, V., Chinnery, P.F., Yu-Wai-Man, P., Kaplan, J., Roubertie, A., Barakat, A., Bonneau, D., Reynier, P., Rozet, J.M., Bomont, P., Hamel, C.P., Lenaers, G. (2015) Recessive Mutations in RTN4IP1 Cause Isolated and Syndromic Optic Neuropathies. American journal of human genetics. 97:754-60.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping