Novel compound heterozygous mutations in <i>CYP1B1</i> identified in a Chinese family with developmental glaucoma

Cai, Suping; Zhang, Daren; Jiao, Xiaodong; Wang, Tingting; Fan, Mengjie; Wang, Yun; Hejtmancik, J. F.; Liu, Xuyang

doi:10.3892/mmr.2021.12443

Cited by 4 publications

(4 citation statements)

References 31 publications

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“…The new c.1310C>G variant represents a change from Proline into Arginine at position 437. Interestingly, mutations affecting the same position have been reported before in patients from diverse ethnic background, for example, Proline was mutated into Leucine (p.P437L) in PCG patients from Turkey (Stoilov et al, 1998), Brazil (Stoilov et al, 2002), Pakistan (Rashid et al, 2019), Siberia (Ivanoshchuk et al, 2020) and China as well (Cai et al, 2021). In the same context, Proline was also mutated into Alanine (p.P437A) in a Tunisian patient (Bouyacoub et al, 2014).…”

Section: Discussionmentioning

confidence: 74%

A novel missense variant in CYP1B1 in an Egyptian patient with Primary Congenital Glaucoma

Elkhouly

Amer²,

Ismail³

et al. 2022

Middle East Journal of Medical Genetics

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Background: Primary Congenital Glaucoma (PCG) is a critical disease that can lead to blindness if left untreated. It is considered the most common type among pediatric glaucoma cases. Mutations in CYP1B1 gene are the predominant cause for the disease in most cases especially in the Middle East and North Africa regions where high consanguinity rates are reported. Purpose: Reporting a new PCG case from Egypt harboring a novel variant in CYP1B1. Patients and Methods:The patient underwent a full clinical examination, reporting visible symptoms, and measuring both eyes' IOP and corneal diameter. Genetic testing of CYP1B1 was performed using Sanger sequencing. Results: The patient was found to carry compound heterozygous missense variants: c.1310C>G (p.P437R) and c.1320T>G (p.F440L). Of them, the c.1310C>G (p.P437R) was not reported before. Conclusions: We detected a new variant in CYP1B1 expanding the mutational spectrum of this rare disorder. Further, identifying an additional case with biallelic CYP1B1 variants strongly supports the critical role this gene possesses to PCG phenotype.

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Section: Discussionmentioning

confidence: 74%

A novel missense variant in CYP1B1 in an Egyptian patient with Primary Congenital Glaucoma

Elkhouly

Amer²,

Ismail³

et al. 2022

Middle East Journal of Medical Genetics

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“…Its increased expression in fetal eyes as compared to adult eyes suggests its significance in the development of childhood glaucoma specifically [190]. Numerous case reports have highlighted the incidence of bilateral PCG in those with homozygous or compound heterozygous CYP1B1 variants in individuals both with and without a family history of the disease, with the most common variants being p.G61E, p.R368H, pE229K, and p.R390H [26][27][28][29][30][31][32][33][34][35][36].…”

Section: Cyp1b1mentioning

confidence: 99%

Genetic changes and testing associated with childhood glaucoma: A systematic review

Kumar,

Han,

Oatts

2024

PLoS ONE

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Many forms of childhood glaucoma have been associated with underlying genetic changes, and variants in many genes have been described. Currently, testing is variable as there are no widely accepted guidelines for testing. This systematic review aimed to summarize the literature describing genetic changes and testing practices in childhood glaucoma. This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic review and Meta-Analyses (PRISMA) 2020 guidelines and registered with Prospero (ID CRD42023400467). A comprehensive review of Pubmed, Embase, and Cochrane databases was performed from inception through March 2, 2023 using the search terms: (glaucoma) AND (pediatric OR childhood OR congenital OR child OR infant OR infantile) AND (gene OR genetic OR genotype OR locus OR genomic OR mutation OR variant OR test OR screen OR panel). Information was extracted regarding genetic variants including genotype-phenotype correlation. Risk of bias was assessed using the Newcastle-Ottawa Scale. Of 1,916 records screened, 196 studies met inclusion criteria and 53 genes were discussed. Among study populations, mean age±SD at glaucoma diagnosis was 8.94±9.54 years and 50.4% were male. The most common gene discussed was CYP1B1, evaluated in 109 (55.6%) studies. CYP1B1 variants were associated with region and population-specific prevalence ranging from 5% to 86% among those with primary congenital glaucoma. MYOC variants were discussed in 31 (15.8%) studies with prevalence up to 36% among patients with juvenile open angle glaucoma. FOXC1 variants were discussed in 25 (12.8%) studies, which demonstrated phenotypic severity dependent on degree of gene expression and type of mutation. Overall risk of bias was low; the most common domains of bias were selection and comparability. Numerous genes and genetic changes have been associated with childhood glaucoma. Understanding the most common genes as well as potential genotype-phenotype correlation has the potential to improve diagnostic and prognostic outcomes for children with glaucoma.

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“…Here in two families PCG049 and PCG062, we identified compound heterozygous mutations in CYP1B1 gene. Previously compound heterozygosity has been reported in developmental glaucoma, [45] and primary congenital glaucoma patients from China [46]. Cai et al, 2021 reported that two heterozygous mutations c.1310C>T (p.P437L) and c.3G>A (p.M1I) are responsible for glaucoma in a Chinese family [45].…”

Section: Plos Onementioning

confidence: 99%

“…Previously compound heterozygosity has been reported in developmental glaucoma, [45] and primary congenital glaucoma patients from China [46]. Cai et al, 2021 reported that two heterozygous mutations c.1310C>T (p.P437L) and c.3G>A (p.M1I) are responsible for glaucoma in a Chinese family [45]. 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].…”

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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Novel compound heterozygous mutations in CYP1B1 identified in a Chinese family with developmental glaucoma

Cited by 4 publications

References 31 publications

A novel missense variant in CYP1B1 in an Egyptian patient with Primary Congenital Glaucoma

A novel missense variant in CYP1B1 in an Egyptian patient with Primary Congenital Glaucoma

Genetic changes and testing associated with childhood glaucoma: A systematic review

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

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