OPA1 (Kjer type) dominant optic atrophy: a novel mitochondrial disease

Mol Genet Metab. 2002 Feb;75(2):97-107. doi: 10.1006/mgme.2001.3278.


Dominant optic atrophy (DOA) is the most common form of inherited optic neuropathy. Although heterogeneous, a major locus has been mapped to chromosome 3q28 and the responsible gene, OPA1, was recently identified. OPA1 is a mitochondrial dynamin-related GTPase implicated in the formation and maintenance of the mitochondrial network. To date, 62 mutations have been identified in a total of 201 DOA patients. Most of them (90%) are distributed from exons 8 to 28 with a majority in the GTPase domain (54%). None were found in the alternatively spliced exons 4, 4b, and 5b. Half of them are truncative mutations (50%) with a frequent recurrent allele, c.2708delTTAG. Most missense mutations (81%) cluster within the putative GTPase domain. Various pathogenic mechanisms may play a role in OPA1 DOA. Truncative mutations in the N-terminal region and perhaps missense mutations in the GTPase domain lead to a loss of function of the encoded protein and haplotype insufficiency. However, there is a cluster of truncation mutations in the in C-terminus, a putative dimerization domain, that could act through a dominant negative effect. The findings that OPA1-type DOA, as Leber optic neuropathy, is caused by the impairment of a mitochondrial protein address the question of the vulnerability of the retinal ganglion cell in response to mitochondrial defects.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Chromosomes, Human, Pair 3*
  • GTP Phosphohydrolases / genetics*
  • Humans
  • Mitochondrial Diseases / genetics*
  • Mutation*
  • Optic Atrophy, Autosomal Dominant / genetics*
  • Retinal Ganglion Cells / physiology
  • Sequence Deletion


  • GTP Phosphohydrolases
  • OPA1 protein, human