Last update: 05/06/2006
Background to disease
OMIM # 165500 (OPA1 gene OMIM *605290)
Autosomal dominant optic atrophy (ADOA) or Kjer’s disease is characterised by moderate severe loss of visual acuity with onset in early childhood, blue yellow dyschromatopsia and central scotoma. There is considerable inter- and intra- familial phenotypic variation, with penetrance estimates as low as 40% in some cases. Estimated incidence is between 1:10,000 (Denmark) and 1:50,000 world wide.
The underlying defect is retinal ganglion cell degeneration associated with optic atrophy, as observed in Leber’s Hereditary Optic Atrophy (LHON). LHON has sudden onset visual loss in both eyes asynchronously and appears later in age (18-35 ys).
LHON and ADOA are difficult to distinguish without a family history. LHON is maternally transmitted and due to mutations in mitochondrial DNA (see mitochondrial diseases entry). ADOA can be caused by mutations in two loci, OPA1 (a dynamin-related GTPase involved in mitochondrial biogenesis) on 3q28, and OPA4 on 18q12. The majority of families are linked to OPA1. The gene comprises 29 exons, 28 of which are coding and has two additional alternatively spliced exons. Most mutations cluster in exons 8-16 (GTPase domain) and exons 27-28 (3’ end of the coding region). ~50% mutations cause premature truncation of OPA1.
Laboratory Analysis
Contact scientist: Rachel Robinson
|
|
Test |
Target reporting time (working days) |
|
1. |
Sequence analysis of exons 8,9,12,27 of OPA1a |
40 days |
| 2. | MLPA analysis of OPA1 | under development |
aAnalysis will detect ~55% of mutations reported in patients of European origin (Toomes et al. Hum Mol Genet 10:1369-1379) and 30% of mutations reported on the online database for OPA1 mutations (www.lbbma.univ-angers.fr/eOPA1).