Fatemeh Arab, Esmat Rigi Yousefabadi, Ramin Daneshvar and Ehsan Ghayoor Karimiani
Background purpose: Primary Congenital Glaucoma (PCG) is typically an autosomal recessive trait and is more prevalent in community with consanguineous marriage. The aim of current study was to screen 27 familial cases of PCG for CYP1B1, to identify and determine common mutations, and to understand its penetrance and prevalence in the Eastern provinces of Iran.
Methods: Detailed family histories up to three generations were taken, and pedigree charts were constructed. Genomic DNA was extracted from peripheral leukocytes. Primers were designed for the two coding exons of the CYP1B1 gene and the amplified products were sequenced. PolyPhen and SIFT were used to predict the functional impact of novel mutations identified in this study.
Results: Seventeen of 27 subjects (62.96%) had mutations in the CYP1B1 gene. In this study, 10 specific mutations associated with disease phenotypes were found. Six missense (p. R368H, p.E229K, p.R390C, p.V364M, p.F445I, p.G61E) and one deletion mutation (c.1504_1504delA) were previously reported and 3 missense mutations (p.L480p, p.S476P and p.R175P) were novel. The most common mutation was G61E, which was identified in 8 of 17 cases (47.05%). We also notified that one of the patients was homozygous for the mutation E229K, and also R390C (tetra-allelic).
Conclusion: Mutations in CYP1B1 was a major finding in our PCG patients. Identifying mutations in subjects at risk of developing glaucoma, particularly among relatives of PCG patients, is of clinical relevance. These findings may help in reducing the disease frequency in familial cases through proper counseling. Such studies will be of benefit in the identification of pathogenic mutations in different populations and will enable us to develop simple and rapid diagnostic tests for analyzing such cases.
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