Investigation of mutational spectrum in cytochrome P4501B1 (CYP1B1) as the principal cause of primary congenital glaucoma

Zahid, Tazeen; Khan, Muhammad Umer; Zulfiqar, Aymn; Jawad, Fatima; Saleem, Anosh; Khan, Asia

doi:10.12669/pjms.39.2.7081

Cited by 3 publications

(3 citation statements)

References 19 publications

(24 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Autosomal recessive pathogenic variants of CYP1B1 are the main known cause of PCG, being responsible for up to 85% of cases depending on the population studied. 1,21,22 Rarely, biallelic variants of CYP1B1 have been reported in association with corneal opacities unrelated to the elevated IOP. [2][3][4] Vincent et al described 3 patients with PA, underlying the possible role of CYP1B1 in anterior segment developmental anomalies beyond PCG because one of their patients showed CCO without glaucoma.…”

Section: Discussionmentioning

confidence: 99%

Variable Phenotype of Congenital Corneal Opacities in Biallelic CYP1B1 Pathogenic Variants

Franco,

Gagrani,

Scanga

et al. 2023

Cornea

View full text Add to dashboard Cite

Purpose: The aim of this study is to describe the variable phenotype of congenital corneal opacities occurring in patients with biallelic CYP1B1 pathogenic variants. Methods: A retrospective chart review was conducted to identify patients with congenital corneal opacities and CYP1B1 pathogenic variants seen at UPMC Children's Hospital of Pittsburgh. Ophthalmic examination, high-frequency ultrasound, anterior segment optical coherence tomography, histopathologic images, and details of genetic testing were reviewed. Results: Three children were identified. All presented with raised intraocular pressure. Two patients showed bilateral limbus-to-limbus avascular corneal opacification that did not resolve with intraocular pressure control; 1 showed unilateral avascular corneal opacity with a crescent of clear cornea, iridocorneal adhesions, iridolenticular adhesions, and classical features of congenital glaucoma in the fellow eye (enlarged corneal diameter, Haab striae, and clearing of the corneal clouding with appropriate intraocular pressure control). The first 2 patients were visually rehabilitated with penetrating keratoplasty. Histopathology revealed distinct features: a variably keratinized epithelium; a thick but discontinuous Bowman-like layer with areas of disruption and abnormal cellularity; Descemet membrane, when observed, showed reduced endothelial cells; and no pathological changes of Haab striae were identified. Two patients had compound heterozygous pathogenic variants in CYP1B1 causing premature stop codons, whereas 1 was homozygous for a pathogenic missense variant. Conclusions: Congenital corneal opacities seen in biallelic CYP1B1 pathogenic variants have a variable phenotype. One is that commonly termed as Peters anomaly type 1 (with iridocorneal adhesions, with or without iridolenticular adhesions) and the other is a limbus-to-limbus opacity, termed CYP1B1 cytopathy. Clinicians should be aware of this phenotypic variability.

show abstract

Section: Discussionmentioning

confidence: 99%

Variable Phenotype of Congenital Corneal Opacities in Biallelic CYP1B1 Pathogenic Variants

Franco,

Gagrani,

Scanga

et al. 2023

Cornea

View full text Add to dashboard Cite

show abstract

“…В исследовании Т. Zahid и соавт. [30] у 85 % пациентов с ПВГ наблюдалось двустороннее поражение. Генетический анализ выявил 2 миссенс-мутации CYP1B1 (c.355 G/T p.A119S и c.685G/A p.E229K), которые наблюдались у 94 % пациентов.…”

Section: южная азияunclassified

Genetic Epidemiology of Primary Congenital Glaucoma in the World. Part II

Oganezova,

Kadyshev,

Egorov

2024

Oftalʹmologiâ

View full text Add to dashboard Cite

This publication continues a review published in December 2023 about the genetic epidemiology and genotype-phenotype correlations in primary congenital glaucoma (PCG) worldwide, and presents data from East and South Asia, Western Europe and Russia. Analysis of the incidence of PCG data in these regions shows that the rates for Western Europe, the European part of Russia and East Asia are comparable and average 1:10,000–18,000 newborns and higher in ethnically mixed groups. On the territory of South Asia, the minimum number of children with PCG was recorded in Nepal, and the maximum in India. The majority of researchers talk about the predominance of bilateral process in 62 to 99 % cases. As a rule, there is a slight predominance of boys among patients with PCG; authors from India and France report approximately the same number of boys and girls, and German scientists have found a higher prevalence of PCG among girls. If we talk about the phenotype of the disease, almost all researchers note a more severe course in subgroups with the presence of CYP1B1 mutations than in patients who do not have a mutation in this gene. As for the genetic causes of PCG, the most common are mutations in the CYP1B1 gene, accounting for up to a third of cases in India, Pakistan, Western Europe and the European part of Russia. In East Asian patients, mutations in the CYP1B1 gene are most likely not the main ones in the pathogenesis of PCG, because are found much less frequently and often only in one allele. Chinese scientists say that it is necessary to pay attention to mutations TEK and ZC2HC1C, VPS13D, PGF.

show abstract

“…It has been connected to a higher incidence of illnesses like schizophrenia, anxiety, and depression. Different bioinformatics tools were used for the analysis of mutation (Chu et al 2022 ; Farcas et al 2023 ; Hassan et al 2023 ; Ullah et al 2023 ; Zahid et al 2023 ). Particularly, the Met allele is frequently linked to an increased vulnerability to certain illnesses (Shen et al 2018 ).…”

Section: Introductionmentioning

confidence: 99%

In silico analysis of the Val66Met mutation in BDNF protein: implications for psychological stress

Shan,

Khan,

Ishtiaq

et al. 2024

AMB Expr

View full text Add to dashboard Cite

The brain-derived neurotrophic factor (BDNF) involves stress regulation and psychiatric disorders. The Val66Met polymorphism in the BDNF gene has been linked to altered protein function and susceptibility to stress-related conditions. This in silico analysis aimed to predict and analyze the consequences of the Val66Met mutation in the BDNF gene of stressed individuals. Computational techniques, including ab initio, comparative, and I-TASSER modeling, were used to evaluate the functional and stability effects of the Val66Met mutation in BDNF. The accuracy and reliability of the models were validated. Sequence alignment and secondary structure analysis compared amino acid residues and structural components. The phylogenetic analysis assessed the conservation of the mutation site. Functional and stability prediction analyses provided mixed results, suggesting potential effects on protein function and stability. Structural models revealed the importance of BDNF in key biological processes. Sequence alignment analysis showed the conservation of amino acid residues across species. Secondary structure analysis indicated minor differences between the wild-type and mutant forms. Phylogenetic analysis supported the evolutionary conservation of the mutation site. This computational study suggests that the Val66Met mutation in BDNF may have implications for protein stability, structural conformation, and function. Further experimental validation is needed to confirm these findings and elucidate the precise effects of this mutation on stress-related disorders.

show abstract

Investigation of mutational spectrum in cytochrome P4501B1 (CYP1B1) as the principal cause of primary congenital glaucoma

Cited by 3 publications

References 19 publications

Variable Phenotype of Congenital Corneal Opacities in Biallelic CYP1B1 Pathogenic Variants

Variable Phenotype of Congenital Corneal Opacities in Biallelic CYP1B1 Pathogenic Variants

Genetic Epidemiology of Primary Congenital Glaucoma in the World. Part II

In silico analysis of the Val66Met mutation in BDNF protein: implications for psychological stress

Contact Info

Product

Resources

About