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B. Jian Seyedahmadi, E.L. Berson, T.P. Dryja; Screening of 51 Newly Identified USH2A Exons Among Patients With Usher Syndrome Type II and Non–Syndromic Recessive Retinitis Pigmentosa . Invest. Ophthalmol. Vis. Sci. 2005;46(13):1801.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To establish the spectrum of mutations in 51 newly identified USH2A exons (exons 22 to 72) and to measure the proportion of patients with Usher syndrome type II (USH2) or with non–syndromic autosomal recessive retinitis pigmentosa (ARRP) who have mutations in this part of the USH2A gene. Methods: Fragments of the USH2A gene were amplified, some individually and others in small sets, from the leukocyte DNA of 214 unrelated patients with a prior diagnosis of Usher syndrome type II (USH2), and 166 with non–syndromic autosomal recessive retinitis pigmentosa (ARRP). Amplified DNA fragments were scanned for mutations using direct sequencing. Results: A screen (to date) of 16 the 51 exons (31%) revealed 55 sequence variations. Of these, 14 are categorized as definite pathogenic mutations (6 nonsense, 4 frameshift, and 4 intron changes), 20 as of uncertain pathogenicity (all missense), and 21 as non–pathogenic polymorphisms or rare variants (13 isocoding, 6 missense, and 2 intron changes). Of the 214 USH2 patients and 166 ARRP patients studied, 22 have definite mutations including 13 with USH2 (6%) and 9 with ARRP (5%). In 15 patients (68%) the mutation is their first known mutation in the USH2A gene. This includes 8 patients with USH2 (≈ 4%) and 7 patients with ARRP (≈ 4%). We also found the second mutation in 5 patients with USH2 and 2 patients with ARRP who had already had the first mutation identified in exons 1 to 21. Conclusions: In our recent article (Jian Seyedahmadi et al., Exp. Eye Res. 2004; 79:167–173) we found mutations in the first 21 exons of the USH2A gene in 39% of USH2 patients and 12% of ARRP patients. The partial screen of the newly identified exons in this gene has uncovered additional cases with USH2A mutations, so that the estimated percentages are now 43% of USH2 and 16% of ARRP patients. It is expected that these percentages will increase as the remaining exons are evaluated. Mutations in the USH2A gene could be the most common cause of retinitis pigmentosa in North America.
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