Cytochrome P450 1B1 and primary congenital glaucoma

AbstractPrimary congenital glaucoma (PCG) is the most common type of infantile glaucoma, yet it remains a relatively rare disease, because the disease is often transmitted in an autosomal recessive pattern. However, PCG occurs up to 10 times more frequently in certain ethnic and geographical groups where consanguineous relationships are common. The aim of this study was to investigate the distribution of mutations in the cytochrome P450 1B1 gene (CYP1B1) in patients with PCG among different populations around the world from 2011 until May 2016. We referred to the electronic databases, such as Medline, Clinicalkey, Scopus, and ScienceDirect, to search for articles that were published in this area. Nineteen records were included in this qualitative synthesis. CYP1B1 mutations were assessed in 1,220 patients with PCG and identified in 41.6% of them. According to these studies, 99 mutations including 60 novel mutations were found. Nonsignificant difference in the sex ratio has been reported. This current review shows that consanguinity plays an important role in the PCG pathogenesis and transmission; however, sporadic mutations have been found in some cases. A difference in penetrance was highlighted by some mutations. The CYP1B1 mutations were mostly found in the Middle East and the Maghreb with a rate of 64.8 and 54.4%, respectively, followed by Europe (34.7%), Asia (21.3%), and finally the United States (14.9%). Founder mutations in different geographical areas have been discovered. For instance, the p.Gly61Glu, p.Arg390His, p.Gly61Glu, c.4,339delG, p.E387Lys, and p.Val320Leu were considered founder mutations for Iran/Saudi Arabia, Pakistan, Lebanon, Morocco, Europe, and Vietnam/South Korea, respectively. Many common mutations in different countries were found, such as in Morocco, where its mutations were similar to seven other countries. These findings suggest that the ethnic differences and the geographical distribution of PCG give us a large CYP1B1 mutation pattern. Genetic tests looking for founder and common mutations should be the first step in genetic screening for patients with PCG.

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Cytochrome P450 Family 1 B1 Gene Mutations in Primary Congenital Glaucoma Affected Egyptian Patients

Ophthalmology Research An International Journal ◽

10.9734/or/2019/v11i130120 ◽

2019 ◽

pp. 1-11

Author(s):

Amanne Feisal Esmael ◽

Hanaa Abdel-Sadek Oraby ◽

Soheir Mohamed El Nahas

Keyword(s):

Cytochrome P450 ◽

Promoter Region ◽

Genetic Data ◽

Congenital Glaucoma ◽

Sequencing Analysis ◽

Coding Region ◽

Primary Congenital Glaucoma ◽

Cyp1b1 Gene ◽

Egyptian Patients ◽

Cytochrome P450 Family

Aims: Primary congenital glaucoma (PCG) is a leading cause of childhood blindness. The cytochrome P450 family 1, subfamily B, polypeptide 1 (CYP1B1) is the most mutated gene that is associated with PCG. Very few studies have examined the promoter region and exon1 of the CYP1B1 gene. This work was planned to contribute to the description of the possible causative mutations of CYP1B1 gene that are related to PCG affected Egyptian patients. Patients and Methods: Patients diagnosed as glaucomatous based on their symptoms and detailed ophthalmological examinations at the time of presentation underwent an intraocular pressure lowering surgical procedure. Investigations were further proceeded on the molecular level. Sequencing-based mutation screen for the promoter region, exon1 and the coding region of exon3 of CYP1B1 gene have been performed in two related consanguineous PCG affected families and four other sporadic Egyptian patients using the polymerase chain reaction (PCR) assay; where PCR products were sequenced, and further analyzed. Results: Sequencing analysis revealed three novel mutations in PCG affected patients one in the promoter region (g.G2872A) and two in exon1 (g.C3268T and g.C3332T). Two additional mutations in exon3 (p.L432V and p.N453S) reported for the first time in PCG affected Egyptian patients. Clinical and genetic data of the two consanguineous families revealed that although the four parents have the same variations as their sons, they are ophthalmologically free. Conclusion: Regular ophthalmic examinations of siblings and parents of these affected patients should take place for early detection of any form of glaucoma to allow prompt diagnosis and early treatment when needed. Clinical examination and molecular genetic data could contribute to early diagnosis and prevention of the visual impairment caused by PCG. This study provides groundwork for expanded genetic investigations in Egypt paving the way for genetic counseling to help affected families make informed medical and personal decisions.

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Absence of Cytochrome P450-1b1 Increases Susceptibility of Pressure-Induced Axonopathy in the Murine Retinal Projection

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.636321 ◽

2021 ◽

Vol 9 ◽

Author(s):

Naseem Amirmokhtari ◽

Brian D. Foresi ◽

Shiv S. Dewan ◽

Rachida A. Bouhenni ◽

Matthew A. Smith

Keyword(s):

Cytochrome P450 ◽

Superior Colliculus ◽

Axonal Transport ◽

Vision Loss ◽

Cell Structure ◽

Congenital Glaucoma ◽

Retinal Ganglion ◽

Retinal Projection ◽

Cytochrome P450 1B1

Mutations in the cytochrome P450-1B1 (Cyp1b1) gene is a common genetic predisposition associated with various human glaucomas, most prominently in primary congenital glaucoma (PCG). The role of Cyp1b1 in the eye is largely unknown, however, its absence appears to drive the maldevelopment of anterior eye structures responsible for aqueous fluid drainage in murine models. Nevertheless, vision loss in glaucoma ultimately results from the structural and functional loss of retinal ganglion cells (RGCs). Cyp1b1’s influence in the development and support of retinal ganglion cell structure and function under normal conditions or during stress, such as elevated ocular pressure; the most common risk factor in glaucoma, remains grossly unknown. Thus, to determine the role of Cyp1b1 in normal retinal projection development we first assessed the strucutrual integrity of RGCs in the retina, optic nerve, and superior colliculus in un-manipulated (naïve) Cyp1b1-knockout (Cyp1b1–/–) mice. In addition, in a separate cohort of Cyp1b1–/– and wildtype mice, we elevated and maintained intraocular pressure (IOP) at glaucomatous levels for 5-weeks, after which we compared RGC density, node of Ranvier morphology, and axonal transport between the genotypes. Our results demonstrate that naïve Cyp1b1–/– mice develop an anatomically intact retinal projection absent of overt glaucomatous pathology. Following pressure elevation, Cyp1b1–/– accelerated degradation of axonal transport from the retina to the superior colliculus and altered morphology of the nodes of Ranvier and adjacent paranodes in the optic nerves. Together this data suggests the absence Cyp1b1 expression alone is insufficient to drive murine glaucomatous pathology, however, may increase the vulnerability of retinal axons to disease relevant elevations in IOP.

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Meta-analysis of CYP1B1 gene mutations in primary congenital glaucoma patients

European Journal of Ophthalmology ◽

10.1177/11206721211016308 ◽

2021 ◽

pp. 112067212110163

Author(s):

Amine Haddad ◽

Oum Kaltoum Ait Boujmia ◽

Loubna El Maaloum ◽

Hind Dehbi

Keyword(s):

Saudi Arabia ◽

Meta Analysis ◽

Gene Mutations ◽

Severe Form ◽

Congenital Glaucoma ◽

Common Mutation ◽

Primary Congenital Glaucoma ◽

Cytochrome P450 1B1 ◽

Significant Difference ◽

Depth Study

Primary congenital glaucoma (PCG) is a rare and severe form of glaucoma and is usually transmitted as an autosomal-recessive disease. However, PCG is more common in certain ethnic and geographic groups where consanguineous relationships are common. The importance of this review is to inspect the mutations in the cytochrome P450 1B1 gene (CYP1B1) and to highlight the interest of the genetic study of CYP1B1 mutations. An in-depth study was carried out by the following search engines: PubMed, Scopus, clinic key and direct science for articles that have been published from 2011 until 2020. One hundred and sixty-one mutations were found in 1641 tested patients and three families, including 78 novel mutations. We identified a no significant difference in the sex ratio and the bilaterality was reported in the majority of patients. We have shown through this study that inbreeding plays an important role in the pathogenesis of PCG transmission compared to the sporadic mutations that have been found in some cases. The majority of the included studies were from ASIA (64.3%), followed by Europe (17.85%), America (10.71%) and Africa (7.14%). The first and most common mutation in our study is 182 G>A (p.Gly61Glu). It was identified in Iran, Portugal and Saudi Arabia and for the first time in Brazil and Vietnam. The greatest number of mutations in common is p.Gly61Glu. Mainly within five countries: Iran, Portugal, Saudi Arabia, Brazil and Vietnam. The first step in PCG screening should be a genetic test looking for founder and common mutation coupled with a clinical examination.

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