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S. Yao, S. Dharmaraj, T. Millender-Swain, M. ElCherbini, I.H. Maumenee; Mutations in the Gene Encoding RPE65 in Patients With Leber Congenital Amaurosis (LCA) . Invest. Ophthalmol. Vis. Sci. 2003;44(13):2303.
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Purpose: The RPE65 gene was screened for defects in patients with LCA to determine the mutation spectrum, to gain insight into the etiology of this disorder and to identify patients for treatment with novel gene therapies. Methods: DNA was isolated from peripheral blood of 126 unrelated families whose proband was diagnosed with LCA. DNA samples for each of the 14 exons and the promoter region of the gene were PCR amplified and analyzed for possible mutations at optimized temperatures by DHPLC on the Transgenomic WAVE system. Families were of world-wide distribution. Mutations were identified by DNA sequence analysis. Results: Two homozygous and 1 heterozygous missense mutations [A132T (Egypt), A434V (Ghana), R85H (Iran)], were found in exons 4, 5 and 12. One intronic sequence change was found near the donor sequence of intron 11 in a patient from Greece that was absent in over 400 patient and control DNA samples analyzed. Conclusions: While the R85H mutation is novel, both homozygous changes found have been reported in another patient study indicating potential mutation hotspots. In contrast to our previous study, RPE65 mutations account for less than 2 % suggesting an overall incidence of about 6 %.
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