Autosomal Dominant Optic Atrophy: Penetrance and Expressivity in Patients With OPA1 Mutations

OPA1 mutations in Japanese patients suspected to have autosomal dominant optic atrophy

“…To date, over 200 OPA1 mutations have been reported and submitted to the eOPA1 database [8]. OPA1-related ADOA has incomplete penetrance, reported to range from 43 to 90% in several families [5,9,10]. The estimated ADOA prevalence is 1:12,300 for ADOA in Denmark [11] to 1:50,000 and is the most common hereditary optic neuropathy worldwide [12,13].…”

“…ADOA has quite a few characteristic indications: the age of onset is in the early decades of life; the symptoms are relatively insidious; visual acuity (VA) decrease is bilateral and progressive, but there is no acute vision loss; the visual field shows variable centrocecal, either central or paracentral visual field defects and central or centrocecal visual field scotoma is present [2,3]; the optic nerve head shows either temporal or diffuse optic nerve pallor with optic disc excavation [4]; color vision indicates either blue-yellow dyschromatopsia or generalized color vision deficits. Intra-and interfamilial clinical variability and an incomplete penetrance are estimated to occur in about 90% of the familial forms of the disease [5]. Extensive ophthalmic examination of the patients rules out any evidence of glaucomatous, inflammatory, ischemic, toxic or nutritional causes of bilateral optic neuropathy.…”

Multiethnic involvement in autosomal-dominant optic atrophy in Singapore

“…It encodes a mitochondrial dynamin-related GTPase critical to mitochondrial function. 3,4 Despite the reported autosomal-dominant inheritance, there is incomplete penetrance of the condition 8 and almost half of the OPA1 mutations have been detected in apparently sporadic cases with no demonstrable family history. 9 As a result of the wide spectrum of mutations, there is considerable inter and intrafamilial variability in the ADOA phenotype ranging from minimal to significant visual loss to severe phenotypes affecting young adults with systemic associations such as sensorineural deafness, ataxia, external ophthalmoplegia, peripheral neuropathy, and myopathy, also known as the ADOA 'plus' phenotypes.…”

Molecular screening of 980 cases of suspected hereditary optic neuropathy with a report on 77 novelOPA1mutations

“…The disease is generally diagnosed in early childhood and is characterized by a progressive bilateral decrease of visual acuity, blue-yellow dyschromatopsia or generalized color vision deficits, variable centrocecal, central or paracentral visual field defects, and temporal or diffuse optic nerve pallor with optic disc excavation (Kerrison, 2001). ADOA is associated with a marked intra-and interfamilial clinical variability and an incomplete penetrance, estimated at about 90% in the familial forms of the disease (Cohn et al, 2007). Mutations in the optic atrophy 1 gene (OPA1; MIM# 605290), located on chromosome 3q28-q29, are responsible for about 60-80% of the cases of ADOA (Alexander et al, 2000;Amati-Bonneau et al, 2005;Delettre et al, 2000;Kjer et al, 1983).…”