Patients in whom CYP1B1 mutations were detected tended to have a more severe phenotype as evidenced by earlier age at diagnosis, higher rate of bilateral disease, and higher number of glaucoma surgeries than those in whom no CYP1B1 mutations were present.
The subnetwork from this analysis suggests a cpAOP that includes changes in CYP1B1 expression, which has been previously established in the literature as a primary cause of glaucoma.
The molecular diagnosis for glaucoma included two cases with compound heterozygous or homozygous pathogenic alleles in CYP1B1 and one family with a dominant pathogenic variant in FOXC1; the second genetic diagnosis for the additional systemic features included compound heterozygous mutations in NPHS1 in one family and a heterozygous 18q23 deletion in another pedigree.
CYP1B1 mutation related congenital glaucoma can present with an extreme form of anterior segment dysgenesis that includes recalcitrant glaucoma, corneal opacification and aniridia.
Seven out of one hundred fifteen (6.1%) individuals had at least one pathogenic or hypomorphic CYP1B1 allele associated with GS, POAG (5) and PXG phenotypes, including two novel sequence variations (p.Ser6Gly, p.Val243Leu).No pathogenic MYOC change was detected.
Hence any mutation in CYP1B1 that reduces its 17β estradiol metabolizing activity might lead to MYOC upregulation, which in turn might play a role in glaucoma pathogenesis.
Mild iris ectropion with partial aniridia in a newborn with glaucoma suggests mutations in CYP1B1 rather than in other genes associated with anterior segment dysgenesis.
Eight further children with CYP1B1 mutations who had CCO from birth and glaucoma underwent successful glaucoma treatment but had persistent diffuse CCO without iridocorneal or keratolenticular adhesions.
The frequency of CYP1B1 variants on direct sequencing of the entire coding region was compared in 399 unrelated German patients with POAG (270, POAG; 47, JOAG; and 82, NTG) and 376 control subjects without any signs of glaucoma on ophthalmic examination.
At least 57% of the PCG nonpenetrant individuals examined clinically were affected with JOAG or POAG to varying degrees, and overall penetrance of "affected CYP1B1 genotypes" with respect to glaucoma may be more than 90%.
The rapidly developing area of stem cell research suggests a potential therapeutic approach for glaucomas resulting from deleterious mutations in CYP1B1, that is, the transfer of stem cells, differentiated to a specific lineage, containing wild-type CYP1B1 to specific regions of the eye, where they will develop into normal cells of that region and rectify the defect.