Direct sequencing of the CYP1B1 gene revealed a novel 3' splice acceptor site causative variant segregating in an autosomal recessive manner in a large consanguineous family with four PCG-affected individuals.
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.
Three distinct levels interact sequentially to produce PCG: (i) genetic mutations mainly affecting the CYP1B1 gene, (ii) absence or dysregulation of a morphogen, and (iii) trabecular meshwork pathological changes either in patterning or remodeling.
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.
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.
The results showed that no deleterious mutations were found in coding regions of LTBP2 in patients with PCG, suggesting that it is not a causal gene for PCG in the Han Chinese population.
DNA sequencing analysis of the CYP1B1 gene was used to screen 21 children with PCG followed on Paediatric Ophthalmology and Medical Genetics consultations at D. Estefânia's Hospital (Centro Hospitalar de Lisboa Central, Portugal).
Patients with unilateral or bilateral PCG diagnosed at the American University of Beirut Medical Center and their first-degree relatives (parents and siblings) were screened for CYP1B1 and MYOC mutations.
A clinical and molecular genetic study was performed on a cohort of 17 patients with PCG and known CYP1B1 mutation profile including 10 subjects with and 7 cases without mutations.
In this study, we assessed the relationship between PCG and FOXC1 variants by Sanger sequencing the proximal promoter and transcribed sequence of FOXC1 from a cohort of 133 PCG families with no known CYP1B1 or MYOC mutations.
Mutations in CYP1B1 result in primary congenital glaucoma (PCG) by an autosomal recessive mode of inheritance while it acts as a modifier locus for primary open angle glaucoma (POAG).
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.
CYP1B1 mutations are the cause of disease in a notable fraction of primary congenital glaucoma (PCG) patients and in a smaller fraction of primary open angle glaucoma (POAG) patients.
Genotype-phenotype correlations was undertaken on clinically well characterized PCG cases from India (n=301) and Brazil (n=150) to assess the contributions of CYP1B1 mutation on a set of demographic and clinical parameters.