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Maria K. Gemenetzi, Andrew J. Lotery; Phenotype/genotype Correlation In A Case Series Of Stargardt Patients With Confirmed ABCA4 Mutations From Southampton, U.K. Invest. Ophthalmol. Vis. Sci. 2012;53(14):4566.
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To investigate phenotypic variability in terms of best corrected visual acuity (BCVA) in patients with Stargardt disease (STGD) and confirmed ABCA4 mutations.
We analyzed the entire coding region of the ABCA4 gene by direct sequencing of seven patients with clinical findings of STGD who were seen in the Retina Clinics of Southampton Eye Unit (Southampton, U.K) between 2002 and 2011. Phenotypic variables recorded included: BCVA, fluorescein angiographic appearance, electrophysiology and visual fields. We estimated disease duration based on the date of first time diagnosis of the disease by a retina specialist.
The patients’ age ranged from 30 to 55 years. Four of them were male and three were female. Disease duration varied between 0 and 22 years. BCVA ranged from 0.02 to 1.34 logMAR. All patients were found to have in heterozygous form amino acid-changing variants (missense mutations) in the ABCA4 gene. A splice sequence change was additionally found in a 30 year old patient with severly affected vision. One missense mutation found in a mildly affected 44 year old patient recently diagnosed with STGD has not been described in the literature. A frameshift mutation also not identified before was found in a severly affected 34 year old patient diagnosed with STGD only a year previously.
The identified ABCA4 mutations in all patients were compatible with the resulting phenotypes in terms of visual acuity. Higher BCVAs were recorded in patients with missense mutations and a short duration of the disease as expected. A novel frameshift mutation in the ABCA4 gene, 6709insA, may account for a rapid reduction in visual acuity and may therefore be correlated with a severlyaffected phenotype. Our small case series of STGD patients contributes to the definition of the genotype/phenotype relationship. This information may prove useful in the selection of candidates for clinical trials in ABCA4 disease.
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