Autoomal Dominant Optic Atrophy: Penetrance and Expreivity in Patient With OPA1 Mutation Original Reearch Article

Purpoe We identified familie with autoomal dominant optic atrophy (ADOA), determined the number and type of OPA1 mutation, and invetigated the phenotypic variation and penetrance in ADOA Autralian pedigree. Deign Cro-ectional genetic tudy. Method Proband were identified on the bai of characteritic clinical feature of ADOA. We creened the OPA1 gene uing ingle-trand conformational polymorphim, heteroduplex analyi (CP/HA), or by direct equencing. Penetrance for pedigree in which a mutation of OPA1 had been identified wa calculated initially uing all recruited individual, and ubanalyi wa performed uing only thoe familie for which there wa total recruitment of ibling. Reult A total of 406 patient from 17 pedigree were recruited, and OPA1 mutation were identified in 11/17 (65%) of thee. The mean age at clinical examination wa 38.2 ± 19.9 year (median age, 35 year; range, four to 83 year). The median bet-corrected viual acuity in OPA1-mutation carrier wa 20/70 (range, 20/16 to hand movement [HM]). The penetrance in Autralian ADOA pedigree in the familie with complete ibling recruitment wa 82.5%. On the other hand, overall penetrance for all individual harboring an OPA1 mutation wa 88%. Concluion OPA1 mutation were identified in 11/17 (65%) of the ADOA pedigree in thi tudy. The penetrance in our cohort wa lower than originally decribed (82.5% v 98%) but higher than ome recent tudie ince the availability of genotyping. It i anticipated that thi figure would be even lower a more aymptomatic individual are identified. There are likely to be other genetic and environmental modifier influencing dieae penetrance.