Autosomal dominant Optic Atrophy: Genetic causes and their consequences
Molekulargenetisches Labor, Universitäts-Augenklinik Abt.2, Tübingen
Purpose: Review about the genetic basis and aspects of autosomal dominant optic atrophy (adOA) and the current knowledge about the function of the OPA1 gene.
Method: Molecular genetic analysis of the OPA1 gene in families with adOA. Expression analysis of the OPA1 gene in the retina. Biochemical und cell biological investigations about the localization and function of the OPA1 gene product.
Results: Mutations in the OPA1 (optic atrophy 1) gene are a main cause of adOA. Depending on the inclusion criteria OPA1 gene mutations can be identified in 35-60% of all patients with a clinical diagnosis of adOA. However, in some adOA families involvement of the OPA1 gene can be definitely excluded. More than 60 different mutations in the OPA1 gene have been reported up-to-now. The majority of mutations represent insertions or deletions, stop- and splice site mutations, that result in a truncated polypeptide. Therefore, haploinsufficiency has been proposed as the main disease mechanism. The clinical expression is highly variable and gene carriers without clinical symptoms even in adulthood are not rare. The OPA1 gene encodes a polypeptide with structural similarity to the dynamin protein family. It has been shown to be imported into mitochondria and there localizes to the outer face of the inner membrane. The OPA1 protein is presumably involved in membrane fusion processes between mitochondria or the formation of cristae s
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