These results confirm the pathogenicity of the analysed missense CYP1B1 variants and further support the concept that either absent or very low CYP1B1 activity levels are the primary molecular defect involved in PCG pathogenesis.
We present a comprehensive sequence analysis of the translated regions of the CYP1B1 gene in 22 PCG families and 100 randomly selected normal individuals.
Our results suggest primary congenital glaucoma and the anterior segment dysgenesis disorders may share a common molecular pathophysiology in the CYP1B1 pathway.
Overall, our data suggest that interaction of TEK and CYP1B1 contributes to PCG pathogenesis and argue that TEK-CYP1B1 may perform overlapping as well as distinct functions in manifesting the disease etiology.
The gene CYP1B1 at GLC3A was screened in 19 Iranian PCG probands who had been recruited mostly from among individuals of Turkish ethnicity and individuals from central and eastern Iran.
Similar analysis will be helpful in understanding of the biological role of CYP1B1 and the effect of mutations on the regulatory and enzymatic functions of CYP1B1 that result in PCG.
Our results support the premise that CYP1B1 is a major gene for PCG, appearing to be responsible for the disease in roughly one in six Chinese PCG patients.
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.
CYP1B1-deficient mice exhibit abnormalities in their ocular drainage structure and trabecular meshwork that are similar to those reported in human PCG patients.
The fact that this dysmorphic girl is Saudi Arabian and has CYP1B1-negative primary congenital glaucoma suggests that her glaucoma phenotype is related to her de novo copy number variation.