Homozygous p.G61E mutation in a consanguineous Pakistani family with co-existence of juvenile-onset open angle glaucoma and primary congenital glaucoma

Bashir, Rasheeda; Tahir, Hafsa; Yousaf, K.; Naz, Shagufta; Naz, Sadaf

doi:10.1016/j.gene.2015.07.014

Cited by 12 publications

(7 citation statements)

References 14 publications

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“…The presence of p.E229K variant in glaucoma‐affected and clinically normal individuals among ethnically similar and different patients may be due to either nonpenetrance or variable expressivity. Such findings regarding different CYP1B1 mutations (eg, p.A115P) have been already described in glaucoma patients from Pakistani, Saudi Arabian, and Iranian populations respectively …”

Section: Discussionsupporting

confidence: 66%

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Mutational analysis of the CYP1B1 gene in Pakistani primary congenital glaucoma patients: Identification of four known and a novel causative variant at the 3′ splice acceptor site of intron 2

Afzal

Firasat

Kaul

et al. 2018

Congenital Anomalies

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Funding informationQuaid-i-Azam University Primary congenital glaucoma (PCG) causes blindness in early age. It has an autosomal recessive pattern of inheritance, hence is more prevalent in populations with frequent consanguineous marriages that occur in the Pakistani population. Mutations in the CYP1B1 gene are commonly associated with PCG. The aim of the present study was to identify genetic mutations in the CYP1B1 gene in PCG cases belonging to 38 Pakistani families. DNA was extracted using blood samples collected from all enrolled patients, their available unaffected family members and controls. Direct sequencing of the CYP1B1 gene revealed a novel 3' splice acceptor site causative variant segregating in an autosomal recessive manner in a large consanguineous family with four PCG-affected individuals. The novel variant was not detected in 93 ethnically matched controls.Furthermore, four already reported mutations, including p.G61E, p.R355X, p.R368H, and p. R390H were also detected in patients belonging to nine different families. All identified causative variants were evaluated by computational programs, that is, SIFT, PolyPhen-2, and Muta-tionTaster. Pathogenicity of the novel splice site variant identified in this study was analyzed by Human Splicing Finder and MaxEntScan. Ten out of 38 families with PCG had the disease due to CYP1B1 mutations, suggesting CYP1B1 was contributing to PCG in these Pakistani patients.Identification of this novel 3' splice acceptor site variant in intron 2 is the first report for the CYP1B1 gene contributing to genetic heterogeneity of disease. K E Y W O R D S autosomal recessive, CYP1B1, primary congenital glaucoma, splice site variant

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Section: Discussionsupporting

confidence: 66%

“…In a report from the Pakistani population, the heterozygous p.G61E variant was associated with POAG in a sporadic case . Whereas, reported the homozygous p.G61E variant both in JOAG and PCG patients belonging to a consanguineous Pakistani family. Interestingly, a heterozygous carrier in their analyzed family had no symptoms of glaucoma.…”

Section: Discussionmentioning

confidence: 93%

Mutational analysis of the CYP1B1 gene in Pakistani primary congenital glaucoma patients: Identification of four known and a novel causative variant at the 3′ splice acceptor site of intron 2

Afzal

Firasat

Kaul

et al. 2018

Congenital Anomalies

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“…In heterozygous form, p.G61E has been reported with mild phenotype in PCG and POAG patients of different ethnicities (Khan et al, 2011;López-Garrido et al, 2015;Wiggs & Pasquale, 2017). Previously, our study demonstrated that the p.G61E variant was segregated in a consanguineous Pakistani family with co-existence of JOAG and PCG in two successive generations (Bashir et al, 2015). Only one study showed heterozygous p.G61E mutation in sporadic POAG patients from Pakistan (Micheal et al, 2014).…”

Section: Ophthalmic Geneticsmentioning

confidence: 53%

“…In a report from the Pakistani population, the heterozygous p.G61E variant was reported in sporadic cases of POAG (Micheal et al, 2014). Moreover, in our previous study from Pakistan we reported the homozygous p.G61E variant, which, co-segregating in two generations of JOAG and PCG patients from a consanguineous family, showed a severe phenotype with variable penetrance of this p.G61E variant (Bashir et al, 2015).…”

Section: In Silico Analysismentioning

confidence: 84%

High prevalence of glaucoma-associated CYP1B1 mutation (p.G61E) in primary congenital and open angle glaucoma patients in Pakistan

Yousaf¹,

Bashir²,

Balqees³

et al. 2022

J. Natn. Sci. Foundation Sri Lanka

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The purpose of this research study was to investigate the prevalence of the p.G61E variant of the CYP1B1 gene among primary congenital and open angle glaucoma (PCG and POAG) patients in the province of Punjab, Pakistan. A total of 112 POAG and 50 PCG patients were enrolled in this study. Detailed clinical examination was carried out on all patients. Screening of G61E was done by direct Sanger sequencing. Different in silico tools, e.g., Clustal Omega, PSIPRED, and Franklin tools were used to check the conservation, secondary structure, and pathogenicity, respectively, of this variant. Sanger sequencing of the whole CYP1B1 gene revealed a homozygous missense transition, c.182G>A, p.G61E in 25/50 (50%) of PCG and in 42/112 (37.5%) of POAG cases, which co-segregated with the disease phenotype. This study revealed that p.G61E is the relatively major contributor of PCG. However, 42 POAG patients harbouring the G61E mutation showed moderate to severe phenotype, suggesting the genetic heterogeneity of this variant in Pakistani population.

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“…CYP1B1 mutations are the prime cause of primary congenital glaucoma in Pakistani patients (Rauf et al, 2016). Also recounted a family from Pakistan in which participants have inherited JOAG and PCG due to a known homozygous mutation in CYP1B1 (Bashir et al, 2015).…”

Section: Most Frequently Glaucoma Genes Reported In Pakistanmentioning

confidence: 99%

Molecular basis of glaucoma and its therapeutical analysis in Pakistan: an overview

et al. 2017

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The human eye is an organ of vision. It plays a prime role in life, gives us the sense of sight, and enables to understand about the world around us. Visualization and interpretation of colors, shapes and dimensions of numerous objects is made possible by eye. Inherited eye diseases comprise 1/3 of all reported human genetic disorders. This review will focus on Glaucoma which comprises a predictable visual illnesses concerning optic nerve deterioration and if remains without any cure can result in failure in eyesight. The optical nerve injure comprises deterioration of the retinal ganglion cells (RGCs). Glaucoma represents a heterogeneous group of optic neuropathies with a complex genetic basis. These neuropathies gradually reduce vision without warning and often without symptoms. Different forms of glaucoma share some common clinical manifestations that usually include specific abnormal appearance of the optic nerve head, characteristic loss of visual field and chronic painless progression. Glaucoma is a progressive optical neuropathy considered by optical disc changes, nerve fiber film break, and visual field defects. Present-day treatment preferences predominantly targeting at reducing IOP by making use of pharmaceutical means, laser treatment and surgical procedure. Developed conducts target neuroprotection with vaccines, the hang-up of NO synthesis and apoptosis. Attaining a better appreciative of the pathogenesis can support in the improvement of novel handling options and, perhaps, even a remedy for glaucoma. There are more than 1.8million glaucoma patients in Pakistan and almost half of them have already lost their eyesight, permanently, due to delay in diagnosis and treatment. About 90% population in the country has no awareness about this disease, resultantly; more and more people are becoming permanently blind in Pakistan due to untreated glaucoma.

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Homozygous p.G61E mutation in a consanguineous Pakistani family with co-existence of juvenile-onset open angle glaucoma and primary congenital glaucoma

Cited by 12 publications

References 14 publications

Mutational analysis of the CYP1B1 gene in Pakistani primary congenital glaucoma patients: Identification of four known and a novel causative variant at the 3′ splice acceptor site of intron 2

Mutational analysis of the CYP1B1 gene in Pakistani primary congenital glaucoma patients: Identification of four known and a novel causative variant at the 3′ splice acceptor site of intron 2

High prevalence of glaucoma-associated CYP1B1 mutation (p.G61E) in primary congenital and open angle glaucoma patients in Pakistan

Molecular basis of glaucoma and its therapeutical analysis in Pakistan: an overview

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