A novel frameshift founder mutation in the cytochrome P450 1B1 (CYP1B1) gene is associated with primary congenital glaucoma in Morocco: CYP1B1 mutation in PCG patients in Morocco (original) (raw)
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Cytochrome P450 Family 1 B1 Gene Mutations in Primary Congenital Glaucoma Affected Egyptian Patients
Ophthalmology Research: An International Journal
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...
Overview of Cytochrome P450 1B1 gene mutations in patients with primary congenital glaucoma
2011
The objective of this study was to investigate the distribution of mutations in the Cytochrome P450 1B1 gene (CYP1B1) in patients with primary congenital glaucoma (PCG) among different populations. All identifiable original studies on CYP1B1 gene mutations of patients with PCG were reviewed. Finally, DNA mutations within the CYP1B1 gene were identified in 542 patients with PCG according to 52 scientific articles and 147 distinct mutations were found. The 3987G>A (G61E) missense mutation is a founder mutation in Middle Eastern population, responsible for 45.52% of CYP1B1 mutations. In Gypsies, missense mutation 7996G>A (E387K) seems to be a founder mutation, accounting for 79.63% of CYP1B1 mutations. It seems that there is no founder mutation in Asian or Caucasian population, but also accumulates in some spots. Mutations 7927G>A (V364M), 7990C>T (L385F) and 8006G>A (R390H) are common in Asian population. In Caucasians, 7940G>A (R368H), 8037dup10, 8006G>A (R390H), 7901del13, 4340delG, 3987G>A (G61E), 7996G>A (E387K), 4490G>A (E229K) and 8005C>T/A (R390C/S) are common mutations. The findings suggest that ethnic differences and the geographical distribution of PCG may be associated with different CYP1B1 mutation patterns. Such information may be useful in developing strategies for reliable clinical genetic testing of patients with PCG and their families.
Molecular Vision, 2009
Purpose Primary congenital glaucoma (PCG) is an autosomal recessive eye disorder that is postulated to result from developmental defects in the anterior eye segment. Mutations in the cytochrome P4501B1 (CYP1B1) gene are a predominant cause of congenital glaucoma. In this study we identify CYP1B1 mutations in PCG patients. Methods Twenty-three unrelated PCG patients and 50 healthy controls were enrolled in the study. CYP1B1 was screened for mutations by PCR and DNA sequencing. Results DNA sequencing revealed a total of 15 mutations. Out of these, four (p.I94X, p.H279D, p.Q340H, and p.K433K) were novel mutations and five were known pathogenic mutations. Five coding single nucleotide polymorphisms and one intronic single nucleotide polymorphism (rs2617266) were also found. Truncating mutations (p.I94X and p.R355X) were associated with the most severe disease phenotype. It is possible that patients with two null alleles with no catalytic activity may present with a more severe phenotype...
Molecular vision, 2013
To identify myocilin (MYOC) and cytochrome P450, family 1, subfamily B, polypeptide 1 (CYP1B1) mutations in a Spanish population with different clinical forms of familial glaucoma or ocular hypertension (OHT). Index patients from 226 families participated in this study. Patients were diagnosed with familial glaucoma or OHT by complete ophthalmologic examination. Screening for MYOC mutations was performed in 207 index patients: 96 with adult-onset primary open-angle glaucoma (POAG), 21 with primary congenital glaucoma (PCG), 18 with juvenile-onset open-angle glaucoma (JOAG), five with Axenfeld-Rieger syndrome (ARS), and 67 with other types of glaucoma. One hundred two of the families (including all those in whom a MYOC mutation was detected) were also screened for CYP1B1 mutations: 45 POAG, 25 PCG, 21 JOAG, four ARS, and seven others. We examined 292 individuals (patients and relatives) with a positive family history of glaucoma or OHT. We identified two novel MYOC variants, p.Lys39A...
Pakistan Journal of Medical Sciences, 2023
Objective: To identify the genetic variants in the CYP1B1 gene associated with Primary Congenital Glaucoma (PCG) and to predict its pathological effect. Method: A descriptive study was conducted in the time period of nine months (September 2021-May 2022) after the ethical approval was taken from The Children Hospital and Institute of Child Health (CH & ICH). Two milliliters of the blood sample from PCG-affected individuals were collected in EDTA vacutainers and genomic DNA was extracted by a phenol-chloroform method. The semi-quantification of extracted DNA was done by agarose gel electrophoresis. PCR amplification was performed by specific primers of CYP1B1 gene then termination sequencing (di-deoxy) was done to detect the genetic variants. Different bioinformatics tools such as BLAST, Ensembl, Clustal Omega, Polyphen and SIFT were used for the further analysis of mutation causing the disease. Results: A total of 85% of patients were bilaterally affected, while 15% were unilaterally affected. Mutation analysis identified five non related known variants. Two missense mutations (c.355 G/T p.A119S and c.685G/A p.E229K) occurred in 94% patients and intragenic SNP occurred in 29% patients along with the 1% somatic (c.693C/A p.F231L) and stop gained mutation (c.840C/A p.C280*). Conclusion: Genetic analysis in the current study showed that 85% of PCG affected patients were due to the CYP1B1 mutation, and disease heterogeneity might be reduced through genetic counseling.
Analysis of CYP1B1 Gene Mutations in Patients with Primary Congenital Glaucoma
Journal of Pediatric Genetics
Primary 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. Th...
Investigation of CYP1B1 mutations in Chinese patients with primary congenital glaucoma
Molecular vision, 2009
This study was conducted to investigate the mutation spectrum of the cytochrome P450 gene (CYP1B1) in Chinese patients with primary congenital glaucoma (PCG). The coding regions of CYP1B1 from 41 Chinese PCG patients were analyzed using polymerase chain reaction (PCR) and heteroduplex analysis-single strand conformation polymorphism (HA-SSCP) followed by subsequent cloning and bidirectional sequencing. New variants were confirmed by restriction fragment length polymorphism (RFLP) analysis in 80 normal Chinese controls. Six distinct mutations, four of which are novel, were identified in 14.6% (6/41) of all patients. The CYP1B1 mutations in two patients were homozygous, and the other four patients were compound heterozygous. Beyond the four novel mutations (g.4531_4552del22bp, g.4633delC, p.S336Y, and p.I471S), two reported missense mutations (R469W and R390H) were also identified. The missense mutation, R390H, was involved in 9.8% (4/41) of patients in our study. None of the novel mu...
Molecular vision, 2010
To investigate the contribution of cytochrome P4501B1 (CYP1B1) and myocillin (MYOC) mutations to primary congenital glaucoma (PCG) in Moroccan families. This study included 90 unrelated families with PCG and 100 normal control individuals. Two previously reported CYP1B1 mutations (g.4339delG and p.G61E) were first screened by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The coding exons of CYP1B1 were sequenced in g.4339delG- and p.G61E-negative or heterozygous probands. Then the coding exons of MYOC were sequenced in patients who had no mutation in CYP1B1 or carried heterozygous CYP1B1 mutation. Twelve CYP1B1 mutations were identified in 43 PCG pedigrees. Three of them were novel (p.R163C, p.C470Y, and g.4330-4331delTG) and associated with moderate to severe phenotypes. Two novel intronic polymorphisms in CYP1B1 were identified in addition to those previously described. The g.4339delG was the most frequent mutation detected in 31 families (34.44%),...