Nuclear gene OPA1, encoding a mitochondrial dynamin-related protein, is mutated in dominant optic atrophy.
Optic atrophy type 1 (OPA1, MIM 165500) is a dominantly inherited optic neuropathy occurring in 1 in 50,000 individuals that features progressive loss in visual acuity leading, in many cases, to legal blindness. Phenotypic variations and loss of retinal ganglion cells, as found in Leber hereditary optic neuropathy (LHON), have suggested possible mitochondrial impairment. The OPA1 gene has been localized to 3q28-q29 (refs 13-19). We describe here a nuclear gene, OPA1, that maps within the candidate region and encodes a dynamin-related protein localized to mitochondria. We found four different OPA1 mutations, including frameshift and missense mutations, to segregate with the disease, demonstrating a role for mitochondria in retinal ganglion cell pathophysiology.
Delettre
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Inserm U. 254, Laboratoire de Neurobiologie de l'audition, Montpellier, France.
Lenaers
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G
Griffoin
J M
JM
Gigarel
N
N
Lorenzo
C
C
Belenguer
P
P
Pelloquin
L
L
Grosgeorge
J
J
Turc-Carel
C
C
Perret
E
E
Astarie-Dequeker
C
C
Lasquellec
L
L
Arnaud
B
B
Ducommun
B
B
Kaplan
J
J
Hamel
C P
CP
D000595:Amino Acid Sequence; D002467:Cell Nucleus / Q000235:genetics; D002874:Chromosome Mapping; D002893:Chromosomes, Human, Pair 3; D034281:Dynamins; D005091:Exons; D005260:Female; D020558:GTP Phosphohydrolases / Q000737:chemistry / Q000235:genetics*; D005799:Genes, Dominant; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008928:Mitochondria / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation; D009896:Optic Atrophy / Q000235:genetics*; D010375:Pedigree; D011110:Polymorphism, Genetic; D012441:Saccharomyces cerevisiae / Q000235:genetics; D012568:Schizosaccharomyces / Q000235:genetics; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
D020558:GTP Phosphohydrolases; C415198:OPA1 protein, human; D034281:Dynamins