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AL Vincent, G Billingsley, A Levin, Y Buys, M Priston, D Williams-Lynn, G Trope, E Heon; Digenic Inheritance of Early Onset Glaucoma: CYP1B1 a Potential Modifier Gene . Invest. Ophthalmol. Vis. Sci. 2002;43(13):3013.
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Purpose: Define the role of MYOC, CYP1B1 and PITX2 in patients with juvenile open angle glaucoma. Methods: We undertook mutational analysis of three glaucoma-related genes (MYOC, CYP1B1 and PITX2)using a combination of single strand conformation polymorphism (SSCP), and direct cycle sequencing. The patient population included 60 unrelated cases affected with JOAG or early onset glaucoma (onset age 5-40 years). Results: MYOC mutations were identified in 8/60 individuals (13.3%); CYP1B1 mutations in 3/60 (5%) and none in PITX2. Individuals with MYOC mutations showed greater phenotypic variability than expected, and included pigment dispersion syndrome and a mixed-mechanism glaucoma. Mutations in CYP1B1 were identified in three cases that did not have features suggestive of congenital glaucoma. Study of one large pedigree with autosomal dominant glaucoma demonstrated segregation of both MYOC and CYP1B1 mutations with the disease. Those who carried the MYOC mutation alone had an average age of onset of 51 years (range 48-64), whereas carriers of both MYOC and CYP1B1 mutations had an average age of onset of 27 years ( range 23 - 38 years) (p= 0.001). Conclusion: This work supports the important role of MYOC in JOAG, but further demonstrates the variability of expression of this gene, as well as the genetic heterogeneity of juvenile glaucoma. We also propose that CYP1B1 may act as a modifier of MYOC expression, and the two genes may interact via a common pathway.
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