A Clinical And Molecular Genetic Study Of Chinese Patients With Primary Congenital Glaucoma

Abstract

Purpose: : Primary congenital glaucoma (PCG) is a devastating automsomal recessive disorder that is associated with developmental defect(s) of the anterior chamber. We conducted this study to clinically characterize Chinese patients with PCG and to determine the role of CYP1B1and MYOC mutations in this cohort.

Methods: : This study included 96 unrelated Han Chinese patients with PCG and 96 ethnically matched, unrelated controls in China. Clinical diagnosis of all subjects was confirmed by a complete ophthalmic examination. All exons of CYP1B1 and MYOC were analyzed by polymerase chain reaction followed by direct DNA sequencing to search for sequence variants. Haplotype analysis and genotype-phenotype correlation analysis were performed.

Results: : Twenty CYP1B1 genomic variations were found in 16 (16.7%) patient and were absent in controls. Ten missense CYP1B1 mutations were found in 6 (6.25%) patients. Among them, five were novel: p. L89P, p.S331I, p.S331I, p.A338P, p.H401D. The patients with CYP1B1 mutations tended to have PCG at an earlier age and were more likely to have bilateral. Twenty-four SNPs in CYP1B1 were identified, 19 of which were novel. Two SNPs (p.R48G and p.A119S) and a common haplotype (5’GTCCTAGC-3’) were found to be significantly associated with PCG. Two novel MYOC variants, i.e., p.A178T and IVS1-48G>A, were identified in two (2.08%) PCG patients but not in controls.

Conclusions: : This study describes the spectrum of CYP1B1 and MYOC mutations in a large cohort of Chinese Han patients with PCG. Our results indicate that only a minor proportion of Chinese PCG patients are caused by CYP1B1 or MYOC mutations. These findings provide further evidence for the genetic heterogeneity and ethnic diversity of PCG in worldwide populations. Other PCG related genes remain to be identified.

Keywords: mutations • genetics • infant vision