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A. Tada, Y. Wada, T. Itabashi, M. Sukegawa, H. Sato, E. Imai, K. Nishida; Mutation Survey of the ABCA4 Gene in Japanese Patients With Stargardt Disease, Cone Rod Dystrophy and Autosomal Recessive Retinitis Pigmentosa . Invest. Ophthalmol. Vis. Sci. 2006;47(13):1695.
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© ARVO (1962-2015); The Authors (2016-present)
To determine the frequency and types of mutations in the ABCA4 gene among Japanese patients with Stargardt disease (STGD), cone rod dystrophy (CRD), and autosomal recessive retinitis pigmentosa (ARRP) to characterize the clinical features of patients with pathogenic mutations in this gene.
The coding sequence and the adjacent flanking intron sequences of all 50 exons of the ABCA4 gene were directly sequenced in 8 unrelated patients with STGD, 82 patients with CRD and 96 patients with ARRP. The clinical findings evaluated at visual acuity, visual field area on the Goldmann perimeter, full–field electroretinogram (ERG) amplitudes, and fluorescein angiography (FA).
38 sequence variants were found. 12 of 38 sequence variants; IVS12+2T>G, Asn933Ile, Arg537Cys, His1838Asp, Thr106Phe, Thr1428Met, His1865Tyr, Val567Met, Ser2255Ile, Arg2149ter, Met1209Thr, Ala1506Val, were considered to be pathogenic because of the same mutations reported as pathogenic, or cosegregate with the phenotype. 26 of 38 sequence variants, which included 5 missense changes, 10 isocoding changes, and 11 intronic changes, were non pathogenic. All patients with STGD had the compound heterozygous pathogenic mutations, ((IVS12+2T>G and Asn933Ile, IVS12+2T>G and His1838Asp (3 patients), Arg537Cys and His1838Asp, Thr106Phe and Asn933Ile (2 patients), His1838Asp and Ser2555Ile)). The compound heterozygous Thr1428Met and His1865Tyr, Met1209Thr and Thr1428Met, and the homozygous Thr1428Met mutations were detected in three CRD patients. No disease causing mutations were found in patients with ARRP. Clinical features in 8 patients with STGD showed clinical variability such as sharply demarcated macular degeneration, diffuse retinal degeneration, and the presence or absence of flecks, although all STGD patients showed dark choroids in FA.
The IVS12+2T>G and His1838Asp mutations were detected in Japanese STGD with relatively high frequency. Clinical variability was observed even among patients who had the same mutation in the ABCA4 gene.
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