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RS Sitorus, MN Preising, SM Ardjo, B Lorenz; CYP1B1 Mutations in Patients with Primary Congenital Glaucoma . Invest. Ophthalmol. Vis. Sci. 2002;43(13):3391.
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Purpose: To analyse the CYP1B1 gene for mutations in patients with Primary Congenital Glaucoma (PCG) from Indonesia, Europe and Africa. Methods: Twenty-one patients with a clinical diagnosis of PCG were collected (11 Indonesian, 9 European and 1 African patient). 36 DNA samples from 21 index cases and 15 relatives were screened using SSCP analysis followed by direct sequencing and/or RFLP screening. Results: Three distinct disease causing mutations (Leu364Met and two deletions: 14017del12bp, 1410del13bp) were identified in six of twenty one patients (28.6%). The Leu364Met mutation has been reported previously in the Japanese population and was identified in four of our index cases (19% of all index cases) all originating from Indonesia (36.4 % of all Indonesian index cases). These patients were diagnosed with severe PCG. Three of them were homozygous for the mutation, and 1 was single heterozygous. 1407del12bp is a novel mutation which causes a frameshift but abolishes 4 amino acid positions from Arg355 to Ala358 inside Helix J of CYP1B1. Additionally, the R48G variant was found in this same patient originating from Germany. The 1410del13bp deletion was found in a patient of Italian descent with no additional disease causing mutation but two benign variants (Leu432Val and IVS1-12t/c). Five additional sequence variations were identified: Arg48Gly, Ala119Ser, Leu432Val, Asn453Ser and a novel IVS1-12t/c, which accounts for 22.2%, 5.5 %, 5.5%, 19.4%, and 36.1% of all analysed alleles, respectively. Conclusions: We have described 3 different mutations in the CYP1B1 gene in PCG patients from Indonesia and Europe. Our results support the notion that the CYP1B1 gene is a major candidate gene for PCG. The Leu364Met mutation was found to be a common mutation in Asian patients associated with a severe phenotype by us and others. This study was supported by a research grant from The Alexander von Humboldt Foundation to RS.
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