Two novel variants in CYP1B1 gene: a major contributor of autosomal recessive primary congenital glaucoma with allelic heterogeneity in Pakistani patients

Waryah, Yar Muhammad; Iqbal, Muhammad Aamir; Sheikh, Shakeel A.; Baig, Muhammad Azhar; Narsani, Ashok Kumar; Atif, Muhammad; Bhinder, Munir Ahmad; Rahman, Attiq Ur; Memon, Azam Iqbal; Pirzado, Muhammad Suleman; Waryah, Ali Muhammad

doi:10.18240/ijo.2019.01.02

Cited by 5 publications

(4 citation statements)

References 22 publications

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“…Идентификация новых мутаций CYP1B1 подтверждает генетическую гетерогенность пакистанских пациентов с ПВГ. Пациенты с миссенс-мутациями демонстрируют тяжелые фенотипические проявления и плохое зрение после хирургических вмешательств по сравнению с пациентами с нуль-аллелями [29].…”

Section: южная азияunclassified

“…Если говорить о фенотипе заболевания, то практически все исследователи отмечают более тяжелое течение в подгруппах с наличием мутаций CYP1B1, чем у пациентов, не имеющих мутации в данном гене. Тяжесть заболевания характеризовалась его дебютом в более раннем возрасте, двусторонним поражением, большим числом требующихся операций и более низкими зрительными функциями после них [7,24,29,37,39,49]. С более тяжелым фенотипом были связаны бόльшее количество мутантных аллелей у одного пациента [7,37], миссенсмутации по сравнению с нуль-аллелями [29], мутации в 444 кодоне гена CYP1B1 [49].…”

Section: западная европаunclassified

“…Тяжесть заболевания характеризовалась его дебютом в более раннем возрасте, двусторонним поражением, большим числом требующихся операций и более низкими зрительными функциями после них [7,24,29,37,39,49]. С более тяжелым фенотипом были связаны бόльшее количество мутантных аллелей у одного пациента [7,37], миссенсмутации по сравнению с нуль-аллелями [29], мутации в 444 кодоне гена CYP1B1 [49].…”

Section: западная европаunclassified

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

Oganezova,

Kadyshev,

Egorov

2024

Oftalʹmologiâ

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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.

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Section: южная азияunclassified

Section: западная европаunclassified

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

Oganezova,

Kadyshev,

Egorov

2024

Oftalʹmologiâ

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“…In another study conducted on 13 Chinese PCG patients, two heterozygous mutations Ala330Phe and Arg390His were detected in a patient and reduced enzymatic activity due to these variants was reported to be the cause of disease [46]. Waryah et al, 2019 identified compound heterozygosity (p.Val364Met along with p.Pro350Thr) in two consanguineous families of PCG belonging to different ethnic groups of Pakistan [47]. Furthermore, previous studies have also reported co-segregation of heterozygous variants of CYP1B1 with heterozygous TEK alleles in PCG cases [48].…”

Section: Plos Onementioning

confidence: 99%

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

Tehreem

Arooj

Siddiqui³

et al. 2022

PLoS ONE

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Background Primary congenital glaucoma (PCG) is a heterogeneous rare recessively inherited disorder prevalent in regions with high consanguinity. Disease phenotype is associated with increased intra ocular pressure and is a major cause of childhood blindness. Sequence variations in Cytochrome P450 1B1 (CYP1B1) gene are a major cause of PCG. Current study was conducted to screen CYP1B1 gene in highly consanguineous PCG affected families from Pakistani population consistent with the autosomal recessive pattern of PCG inheritance. Methods For this study, patients and controls (clinically unaffected individuals of each family) from 25 consanguineous families belonging to Punjab, Baluchistan and Khyber Pakhtunkhwa, Pakistan were recruited through ophthalmologists. DNA was isolated from collected blood samples. Genetic screening of CYP1B1 gene was done for all enrolled families. In-silico analysis was performed to identify and predict the potential disease-causing variations. Results Pathogenicity screening revealed sequence variants segregating with disease phenotype in homozygous or compound heterozygous form in eleven out of 25 analyzed families. We identified a total of sixteen disease causing variants among which five frameshift i.e., c.629dup (p.Gly211Argfs*13), c.287dup (p.Leu97Alafs*127), c.662dup (p.Arg222Profs*2), c.758_759insA (p.Val254Glyfs*73) and c.789dup (p.Leu264Alafs*63), two silent c.1314G>A, c.771T>G and six missense variations c.457C>G (p.Arg153Gly), c.516C>A (p.Ser172Arg), c.722T>A (p.Val241Glu), c.740T>A (p.Leu247Gln), c.1263T>A (p.Phe421Leu), and c.724G>C (p.Asp242His) are previously un reported. However two frameshift c.868dup (p.Arg290Profs*37), c.247del (p.Asp83Thrfs*12) and one missense variant c.732G>A (p.Met244Ile), is previously reported. Furthermore, six polymorphisms c.1347T>C, c.2244_2245insT, c.355G>T, c.1294G>C, c.1358A>G and c.142C>G were also identified. In the intronic region, a novel silent polymorphism i.e., g.35710_35711insT was found in homozygous state. All the newly detected disease-causing variants were negative in 96 ethnically matched controls. Conclusion Among twenty-five screened families, eight families (PCG50, 52–54, 58, 59, 63 and 67) were segregating disease causing variants in recessive manner. Two families (PCG049 and PCG062) had compound heterozygosity. Our data confirms genetic heterogeneity of PCG in Pakistani population however we did not find molecular variants segregating with PCG in fifteen families in coding exons and intron-exon boundaries of CYP1B1 gene. Genetic counseling was provided to families to refrain from practicing consanguinity and perform premarital screening as a PCG control measure in upcoming generations.

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Genetics and Glaucoma: the state of the art

Tirendi,

Domenicotti,

Bassi

et al. 2023

Front. Med.

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Glaucoma is the second leading cause of irreversible blindness worldwide. Although genetic background contributes differently to rare early-onset glaucoma (before age 40) or common adult-onset glaucoma, it is now considered an important factor in all major forms of the disease. Genetic and genomic studies, including GWAS, are contributing to identifying novel loci associated with glaucoma or to endophenotypes across ancestries to enrich the knowledge about glaucoma genetic susceptibility. Moreover, new high-throughput functional genomics contributes to defining the relevance of genetic results in the biological pathways and processes involved in glaucoma pathogenesis. Such studies are expected to advance significantly our understanding of glaucoma’s genetic basis and provide new druggable targets to treat glaucoma. This review gives an overview of the role of genetics in the pathogenesis or risk of glaucoma.

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Two novel variants in CYP1B1 gene: a major contributor of autosomal recessive primary congenital glaucoma with allelic heterogeneity in Pakistani patients

Cited by 5 publications

References 22 publications

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

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

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

Genetics and Glaucoma: the state of the art

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