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Ulrika Kjellstrom, Sten Andreasson; Visual Prognosis and Association Between Geno - and Phenotype in Families with ABCA4 Mutations. Invest. Ophthalmol. Vis. Sci. 2013;54(15):1327.
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© ARVO (1962-2015); The Authors (2016-present)
To evaluate visual outcome and phenotypes in families with ABCA4 mutations.
Three families with one or more members with known homozygous or compound heterozygote ABCA4 mutations were examined with visual acuity (VA), funduscopy and photography, full-field electroretinography (ff-ERG), multifocal ERG (mERG) and optical coherence tomography (OCT). Microarray was used for ABCA4 genotyping (Asper).
In family 1, the proband was homozygote for c768 G>T. Her aunt was compound heterozygote for c768 G>T and c2894 A>G. The proband had low VA, large central scotomas, reduced ff-ERG cone - and mERG responses. She was diagnosed with cone rod dystrophy (CRD). Her aunt was diagnosed with pigmentosa (RP) with low VA, small crescent-shaped visual fields (VF), reduced ff-ERG and mERG. In family 2, the proband was homozygote for c5917del. She was diagnosed with CRD with reduced VA, ff-ERG cone responses and mERG. Her VFs were constricted with large scotomas. Her father and two sisters were compound heterozygote for c5917del and c5882 G>A. The eldest sister was diagnosed with Stargardt disease (STGD) with low VA, central scotomas, normal ff-ERG and reduced mERG. The youngest sister and the father had no symptoms at the age of 12 and 48 respectively. They demonstrated normal ff-ERGs but reduced mERGs. The sister had normal VA and VFs, while the father had low VA and central scotomas. In family 3, the proband was compound heterozygote for c768 G>T and c3113 C>T. She was diagnosed with STGD with VA 0.1, small central scotomas, normal ff-ERG and reduced mERG. Her son had the same findings except for wider scotomas. Three of the patients with progressive disorders (CRD or arRP) were examined repeatedly during 5-15 years and were found to have prolonged implicit times (ITs) of the 30 Hz flicker and mERG. Patients with two mutations in the ABCA4 gene demonstrated attenuated retina on the OCT macular map.
ABCA4 mutations can lead to STGD, CRD or arRP. At the time of diagnose it is hard to predict the severity of the condition only from genotyping. In this study, prolongation of ITs in the ff and/or mfERG seems to be associated with progressive conditions. ABCA4 mutations are common in the population, thus family members can harbor various combinations of mutations resulting in diverse phenotype and prognosis, further emphasizing the importance of both genetic and electrophysiological tests.
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