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Khaled Abu-Amero, Jose Morales, Layla Ali Aljasim, Deepak Edward; CYP1B1 mutations, a major contributor to juvenile-onset open angle glaucoma. Invest. Ophthalmol. Vis. Sci. 2013;54(15):6217.
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© ARVO (1962-2015); The Authors (2016-present)
To describe the genotype and phenotype in 14 unrelated Saudis with juvenile open angle glaucoma (JOAG).
Saudi patients with JOAG were recruited over a three month period. Detailed clinical history, course and genetic history were obtained. Genotyping was performed using PCR and direct Sanger sequencing for cytochrome P450, family 1, subfamily B (CYP1B1), Myocilin (MYOC) and latent-transforming growth factor beta-binding protein 2 (LTBP2) genes in JOAG patients. Additionally, 200 glaucoma-free ethnicity-matched controls were screened for mutations in the CYP1B1 gene.
The mean age of JOAG subject’s was 24 years and 13/14 had bilateral disease. Most patients had high intraocular pressures with moderately severe glaucomatous damage in at least one eye in 9/14 patients. Eleven (78.6%) patients had apparent sporadic inheritance and 3 (21.4%) presented with a family history of glaucoma. Overall, 12 patients (85.7%) had either a pathologic or potentially pathologic CYP1B1 mutation. Nine patients (64.3%) had CYP1B1 mutations in a homozygous status. Eight of these had a non-synonymous (g.3987 G>A; p.G61E) mutation in a homozygous status and one had a silent synonymous mutation (g.8184 C>T). Two patients (14.3%) had the g.3987 G>A mutation in a compound heterozygous status with another CYP1B1 mutation (g.8131 C>G; p.L432V). Two patients (14.3%) had CYP1B1 mutation (g.3987 G>A) in a heterozygous status with no other mutation, while one patient (7.1%) had no mutation(s) after sequencing the full coding region of the CYP1B1 gene. In the controls screened for mutations in the CYP1B1 gene, 14 (7%) had the p.G61E mutation in a heterozygous status with a minor allele frequency (MAF) of 0.035. The p.L432V mutation was detected in 30 (15%) controls in a heterozygous status and 2 (1%) controls in a homozygous status, raising doubts about its pathogenic status. None of the 14 patients had a pathologic-mutation in the MYOC or LTBP2 genes.
CYP1B1 mutant JOAG occurs at a high rate in the Saudi population with JOAG. Myocilin or LTBP2 gene-mutations do not appear to play a role in Juvenile-onset open angle glaucoma in this population. The glaucoma phenotype seen in this group of patients resembles that described previously in JOAG caused by MYOC mutations. A specific genotype-phenotype relationship was not demonstrated.
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