Analysis of copy number variation using whole genome exon-focused array CGH in Korean patients with primary...

Primary congenital glaucoma (PCG) is an autosomal recessive form of glaucoma that manifests within the first year of life and if left untreated, leads to irreversible blindness. Cytochrome P450 1B1 (CYP1B1) is the major gene known to be associated with PCG. The role of the CYP1B1 gene in disease pathogenesis and the relatively low detection rate of CYP1B1 mutations in some populations, especially Asians, remain unexplained. We hypothesized that altered gene dosage of CYP1B1 or anterior segmental dysgenesis causative genes may be involved in the pathogenesis of PCG.

We performed whole genome exon-focused array comparative genome hybridization (aCGH) to identify copy number variation (CNV) in 20 Korean PCG patients and their parents.

We identified 12 patients with at least one rare gene-containing copy number variation each, corresponding to 25 CNVs (5 deletions and 20 duplications) at frequencies of 5-30% in PCG patients and 0% in controls. The 25 CNVs were not located at known chromosomal loci for PCG, namely GLC3A, which harbors CYP1B1 (2p21), GLC3B (1p36.2-p36.1), or GLC3C (14q23), and did not include any target genes associated with PCG or anterior segmental dysgenesis.

Further genetic studies with larger cohorts of patients are necessary to validate our results and to elucidate other genetic mechanisms underlying PCG, because the identified CNVs might be PCG-specific pathogenic variants and may explain the disease pathogenesis of PCG.