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- Title
Mutation spectrum and splicing variants in the OPA1 gene.
- Authors
Delettre, Cécile; Griffoin, Jean-Michel; Kaplan, Josseline; Dollfus, Hélène; Lorenz, Birgit; Faivre, Laurence; Lenaers, Guy; Belenguer, Pascale; Hamel, Christian P.
- Abstract
Optic atrophy type 1 (OPA1, MIM 165500) is a dominantly inherited optic neuropathy that features low visual acuity leading in many cases to legal blindness. We have recently shown, with others, that mutations in the OPA1 gene encoding a dynamin-related mitochondrial protein, underlie the dominant form of optic atrophy. Here we report that OPA1 has eight mRNA isoforms as a result of the alternative splicing of exon 4 and two novel exons named 4b and 5b. In addition, we screened a cohort of 19 unrelated patients with dominant optic atrophy by direct sequencing of the 30 OPA1 exons (including exons 4b and 5b) and found mutations in 17 (89%) of them of which 8 were novel. A majority of these mutations were truncative (65%) and located in exons 8 to 28, but a number of them were amino acid changes predominantly found in the GTPase domain (exons 8 to 15). We hypothesize that at least two modifications of OPA1 may lead to dominant optic atrophy, that is alteration in GTPase activity and loss of the last seven C-terminal amino acids that putatively interact with other proteins.
- Subjects
GENETIC mutation; RNA splicing; BIOLOGICAL variation; EXONS (Genetics); VISUAL acuity; VISION disorders; NUCLEOTIDE sequence; GENETIC disorders
- Publication
Human Genetics, 2001, Vol 109, Issue 6, p584
- ISSN
0340-6717
- Publication type
Article
- DOI
10.1007/s00439-001-0633-y