Study on Cytochrome P450 Family 1 B1 Gene Mutations in Primary Congenital Glaucoma Affected Egyptian Patients | Chapter 6 | Highlights on Medicine and Medical Research Vol. 1

Aims: A leading cause of childhood blindness is primary congenital glaucoma (PCG). In early infancy, primary congenital glaucoma manifests and is characterized by elevated IOP, broad cornea, and Haab striae. Often seen are varying degrees of corneal haze, photophobia, epiphora, and blepharospasm. The most-mutated gene associated with PCG is the cytochrome P450 family 1, subfamily B, polypeptide 1 (CYP1B1). Very few studies have studied the CYP1B1 gene's promoter region and exon1. This study was intended to contribute to the explanation of potential causative CYP1B1 gene mutations associated with Egyptian PCG-affected patients.

Patients and Methods: Patients diagnosed as glaucomatous were subjected to an intraocular pressure lowering surgical procedure based on their symptoms and thorough ophthalmological assessments at the time of presentation. On the molecular stage, investigations were further carried out. Sequencing-based mutation screening was performed in two linked consanguineous PCG affected families and four other sporadic Egyptian patients using the polymerase chain reaction (PCR) assay for the promoter region, exon1 and the exon3 coding region of the CYP1B1 gene; where PCR products were sequenced and further analyzed.

Results: Sequencing analysis identified three novel mutations, one in the promoter region (g.G2872A) and two in exon1 in PCG affected patients (g.C3268T and g.C3332T). For the first time, two additional mutations in exon3 (p.L432V and p.N453S) have been identified in Egyptian patients affected by PCG. Clinical and genetic data from the two consanguineous families showed that they are ophthalmologically free, although the four parents have the same variations as their sons. For early detection of any type of glaucoma, routine ophthalmic examinations of siblings and parents of these affected patients should be performed to allow for prompt diagnosis and early treatment when appropriate.

Conclusion: The present analysis revealed the presence of six distinct mutations distributed between the CYP1B1 gene promoter-exon1 region and the CYP1B1 gene coding region of exon3. Three of these mutations are, to the best of our knowledge, novel mutations identified for the first time in the present research. For early detection and prevention of visual impairment caused by PCG, clinical examination and molecular genetic data could contribute. This research provides the basis for extended genetic research in Egypt, paving the way for genetic therapy to assist impacted families to make educated medical and personal choices.

Author (s) Details

Amanne Feisal Esmael
Department of Ophthalmology, Faculty of Medicine, Cairo University, Cairo, Egypt.

Professor Hanaa Abdel-Sadek Oraby
Department of Cell Biology, Genetic Engineering and Biotechnology Division, National Research Center, Cairo, Egypt.

Prof. Dr. Soheir Mohamed El Nahas
Department of Cell Biology, Genetic Engineering and Biotechnology Division, National Research Center, Cairo, Egypt.

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