BACKGROUND: Pathogenic variations in the ABCA4 gene were originally recognized as genetic background for the autosomal recessive disorders Stargardt disease and fundus flavimaculatus, but have expanded to embrace a diversity of retinal diseases, giving rise to the new diagnostic term, ABCA4-related retinopathy. Diagnostic genotyping of ABCA4 is complicated by the large size of the gene and the existence of approximately 600 known pathogenic variations, along with numerous rare polymorphisms. A commercial diagnostic array-based assay has been developed targeting known mutations, however a conclusive genetic diagnosis must rely on a comprehensive genetic screening as the mutation spectrum of ABCA4-related retinopathies continues to expand. MATERIAL AND METHODS: Among 161 patients with a Stargardt-related phenotype previously assessed with the commercial ABCA4 mutation microarray, we analyzed the ABCA4 gene with High-resolution melting (HRM) in patients in whom the array analysis identified either a heterozygous mutation (n = 50) or no mutation (n = 30). RESULTS: The HRM method detected each of the already known mutations and polymorphisms. We identified the second ABCA4 mutation in 31 of 50 heterozygous patients (62%). Several novel mutations were identified of which four were identified multiple times. The recurrent novel mutations were subsequently assessed among the 30 patients with possible ABCA4-related diseases, previously found to be negative for known ABCA4 mutations by array analysis. In total, 30 different mutations were identified of which 21 have not been described before. CONCLUSION: Scandinavian patients with ABCA4-related retinopathy appear to have a distinct mutation spectrum, which can be identified in patients of diverse clinical phenotypes.
BACKGROUND: Pathogenic variations in the ABCA4 gene were originally recognized as genetic background for the autosomal recessive disorders Stargardt disease and fundus flavimaculatus, but have expanded to embrace a diversity of retinal diseases, giving rise to the new diagnostic term, ABCA4-related retinopathy. Diagnostic genotyping of ABCA4 is complicated by the large size of the gene and the existence of approximately 600 known pathogenic variations, along with numerous rare polymorphisms. A commercial diagnostic array-based assay has been developed targeting known mutations, however a conclusive genetic diagnosis must rely on a comprehensive genetic screening as the mutation spectrum of ABCA4-related retinopathies continues to expand. MATERIAL AND METHODS: Among 161 patients with a Stargardt-related phenotype previously assessed with the commercial ABCA4 mutation microarray, we analyzed the ABCA4 gene with High-resolution melting (HRM) in patients in whom the array analysis identified either a heterozygous mutation (n = 50) or no mutation (n = 30). RESULTS: The HRM method detected each of the already known mutations and polymorphisms. We identified the second ABCA4 mutation in 31 of 50 heterozygous patients (62%). Several novel mutations were identified of which four were identified multiple times. The recurrent novel mutations were subsequently assessed among the 30 patients with possible ABCA4-related diseases, previously found to be negative for known ABCA4 mutations by array analysis. In total, 30 different mutations were identified of which 21 have not been described before. CONCLUSION: Scandinavian patients with ABCA4-related retinopathy appear to have a distinct mutation spectrum, which can be identified in patients of diverse clinical phenotypes.
Authors: Maria Carolina Ortube; Samuel P Strom; Stanley F Nelson; Steven Nusinowitz; Ariadna Martinez; Michael B Gorin Journal: BMC Med Genet Date: 2014-01-20 Impact factor: 2.103
Authors: Fabian Garces; Kailun Jiang; Laurie L Molday; Heidi Stöhr; Bernhard H Weber; Christopher J Lyons; David Maberley; Robert S Molday Journal: Invest Ophthalmol Vis Sci Date: 2018-05-01 Impact factor: 4.799
Authors: Samuel P Strom; Yong-Qing Gao; Ariadna Martinez; Carolina Ortube; Zugen Chen; Stanley F Nelson; Steven Nusinowitz; Deborah B Farber; Michael B Gorin Journal: BMC Med Genet Date: 2012-08-03 Impact factor: 2.103
Authors: Terry A Braun; Robert F Mullins; Alex H Wagner; Jeaneen L Andorf; Rebecca M Johnston; Benjamin B Bakall; Adam P Deluca; Gerald A Fishman; Byron L Lam; Richard G Weleber; Artur V Cideciyan; Samuel G Jacobson; Val C Sheffield; Budd A Tucker; Edwin M Stone Journal: Hum Mol Genet Date: 2013-08-04 Impact factor: 6.150