Mutation spectrum and splicing variants in the OPA1 gene

Hum Genet. 2001 Dec;109(6):584-91. doi: 10.1007/s00439-001-0633-y. Epub 2001 Oct 30.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing / genetics*
  • Amino Acid Sequence
  • Chromosomes, Human, Pair 3
  • Exons / genetics
  • Frameshift Mutation
  • GTP Phosphohydrolases / genetics*
  • Genetic Testing / methods
  • Humans
  • Molecular Sequence Data
  • Mutagenesis, Insertional
  • Mutation, Missense
  • Optic Atrophy, Autosomal Dominant / etiology
  • Optic Atrophy, Autosomal Dominant / genetics*
  • Point Mutation
  • Polymorphism, Genetic
  • Sequence Deletion
  • Sequence Homology, Amino Acid


  • GTP Phosphohydrolases
  • OPA1 protein, human