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.
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
Figures
Show all Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes