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Abstract #18536 Published in IGR 3-3
Digenic inheritance of early-onset glaucoma: CYP1B1, a potential modifier gene
Vincent AL; Billingsley G; Buys Y; Levin AV; Priston M; Trope G; Williams-Lyn D; Heon EAmerican Journal of Human Genetics 2002; 3: 70
'Early-onset glaucoma' refers to genetically heterogeneous conditions for which glaucoma manifests at the age of five to 40 years. and for which only a small subset is molecularly characterized. The authors studied the role of MYOC, CYP1B1, and PITX2 in a population (n = 60) affected by juvenile or early-onset glaucoma from the greater Toronto area. By a combination of single-strand conformation polymorphism and direct cycle sequencing, MYOC mutations were detected in eight (13.3%) of the 60 individuals, CYP1B1 mutations were detected in three (5%) of the 60 individuals, and no PITX2 mutations were detected. The range of phenotypic expression associated with MYOC and CYP1B1 mutations was greater than expected. MYOC mutations included cases of juvenile glaucoma with or without pigmentary glaucoma and mixed-mechanism glaucoma. CYP1B1 mutations involved cases of juvenile open-angle glaucoma, as well as cases of congenital glaucoma. The study of a family with autosomal dominant glaucoma showed the segregation of both MYOC and CYP1B1 mutations with disease; however, in this family, the mean age at onset of carriers of the MYOC mutation alone was 51 years (range, 48-64 years), whereas carriers of both the MYOC and CYP1B1 mutations had an average age at onset of 27 years (range, 23-38 years) (p = 0.001). This work emphasizes the genetic heterogeneity of juvenile glaucoma and suggests, for the first time, that congenital glaucoma and juvenile glaucoma are allelic variants, and the spectrum of expression of MYOC and CYP1B1 mutations is greater than expected. The authors also propose that CYP1B1 may act as a modifier of MYOC expression, and that these two genes may interact through a common pathway.
Dr A.L. Vincent, Department of Ophthalmology, The Hospital for Sick Children, Toronto, Canada
Classification:
1.2 Population genetics (Part of: 1 General aspects)
