Retinal Phenotypes in Patients Homozygous for the G1961E Mutation in the ABCA4 Gene
| Autor: | Tomas R. Burke, Robert K. Koenekoop, Caroline C W Klaver, Alfonso Baldi, F. P. M. Cremers, Jana Zernant, Alessandro Iannaccone, Radha Ayyagari, Carl Schubert, Allison C. Umfress, R. T. Smith, Rando Allikmets, Maria Laura Ciccarelli, Stephen H. Tsang, Gerald A. Fishman |
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| Přispěvatelé: | Burke, Tr, Fishman, Ga, Zernant, J, Shubert, C, Tsang, Sh, Smith, Rt, Ayyagari, R, Koenekoop, Rk, Umfress, A, Ciccarelli, Ml, Baldi, Alfonso, Iannaccone, A, Cremers, Fp, Klaver, Cc, Allikmets, R., Ophthalmology |
| Rok vydání: | 2012 |
| Předmět: |
Pathology
medicine.medical_specialty medicine.diagnostic_test biology Genetics and epigenetic pathways of disease [NCMLS 6] Fundus photography ABCA4 Articles Macular degeneration Fundus (eye) medicine.disease Fluorescein angiography eye diseases Stargardt disease Mutation (genetic algorithm) medicine biology.protein Age of onset |
| Zdroj: | Investigative Ophthalmology and Visual Science, 53, 8, pp. 4458-67 Investigative Ophthalmology and Visual Science, 53, 4458-67 Investigative Ophthalmology & Visual Science, 53(8), 4458-4467. Association for Research in Vision and Ophthalmology Inc. |
| ISSN: | 0146-0404 |
| DOI: | 10.1167/iovs.11-9166 |
| Popis: | PURPOSE. We evaluated the pathogenicity of the G1961E mutation in the ABCA4 gene, and present the range of retinal phenotypes associated with this mutation in homozygosity in a patient cohort with ABCA4-associated phenotypes. METHODS. Patients were enrolled from the ABCA4 disease database at Columbia University or by inquiry from collaborating physicians. Only patients homozygous for the G1961E mutation were enrolled. The entire ABCA4 gene open reading frame, including all exons and flanking intronic sequences, was sequenced in all patients. Phenotype data were obtained from clinical history and examination, fundus photography, infrared imaging, fundus autofluorescence, fluorescein angiography, and spectral domain-optical coherence tomography. Additional functional data were obtained using the full-field electroretinogram, and static or kinetic perimetry. RESULTS. We evaluated 12 patients homozygous for the G1961E mutation. All patients had evidence of retinal pathology consistent with the range of phenotypes observed in ABCA4 disease. The latest age of onset was recorded at 64 years, in a patient diagnosed initially with age-related macular degeneration (AMD). Of 6 patients in whom severe structural (with/ without functional) fundus changes were detected, 5 had additional, heterozygous or homozygous, variants detected in the ABCA4 gene. CONCLUSIONS. Homozygous G1961E mutation in ABCA4 results in a range of retinal pathology. The phenotype usually is at the milder end of the disease spectrum, with severe phenotypes linked to the presence of additional ABCA4 variants. Our report also highlights that milder, late-onset Stargardt disease may be confused with AMD. (Invest Ophthalmol Vis Sci. 2012; 53:4458–4467) DOI:10.1167/iovs.11-9166 |
| Databáze: | OpenAIRE |
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