Analysis of CYP1B1 gene mutations in primary congenital glaucoma patients

Abstract

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.

Mutation screening of the CYP1B1 gene reveals thirteen novel disease-causing variants in consanguineous Pakistani families causing primary congenital glaucoma

“…This membrane bound protein has a transmembrane domain at amino terminal (53 a.a) and a highly conserved cytoplasmic region (480 a.a) that is connected to amino terminal by a proline rich hinge (10 a.a) [16]. Exact function of CYP1B1 in development of eye is uncertain however it is believed that due to mutations in this gene, generation of some important morphogens is affected leading to structural defects in trabecular meshwork and the aqueous humour outflow pathways [5,6,17,18]. Up till now almost 270 mutations are reported in CYP1B1 gene including missense, small deletions, indels, gross deletions and regulatory mutations [19].…”