Optic Atrophy Type Kjer

Autosomal dominant optic atrophy (ADOA) of the Kjer type (OMIM 165500) is the most common hereditary disorder affected the optic nerve. ADOA occurs with an estimated disease prevalence of 1:50,000 (Lyle, 1990) or in Denmark as high as 1:10,000 (Kjer et al, 1996) rendering it the most common hereditary optic neuropathy. It is characterized by onset of the optic atrophy in early childhood with moderated to severe decrease of visual acuity, development of visual field losses (scotoma) of varying extent, dyschromatopsia (most common blue-yellow tritanopia), measurable dysfunction of the optic nerve fibre, and the temporal pallor of the papilla. The disease course is highly variable in expression and shows incomplete penetrance in some families (Kline et al, 1979; Caldwell et al, 1971; Roggeveen et al, 1985) In 1994 a first locus for autosomal dominant optic atrophy type Kjer was located to the long arm of chromosome 3q28-q29, and in 2000 the underlying gene OPA1 was identified in our lab. The gene codes for a dynamic-related GTPase which is ubiquitously expressed (Alexander et al, 2000; Delettre et al, 2000). Genetic screening of the OPA1 gene in our patients with ADOA has resulted in the identification of over 100 different mutations in our patient collection. Detailed immunohistological analysis on the expression of the OPA1 protein in the human brain has shown that OPA1 is not only expressed in all investigated regions but also in all cell types (Bette et al, 2005). In the retina, OPA1 is expressed in almost all neuronal cell types except for the photoreceptors (Pesch et al, 2004). To date only little is known on the function of OPA1. It seems that OPA1 has an essential role in the maintenance of the mitochondrial function (Olichon et al, 2003; Misaka et al, 2002).