Al Shifa Eye Trust Hospital

Rāwalpindi, Pakistan

Al Shifa Eye Trust Hospital

Rāwalpindi, Pakistan
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Micheal S.,COMSATS Institute of Information Technology | Micheal S.,Radboud University Nijmegen | Yousaf S.,COMSATS Institute of Information Technology | Khan M.I.,COMSATS Institute of Information Technology | And 8 more authors.
Molecular Vision | Year: 2013

Purpose: Matrix metalloproteinases (MMPs) play an important role in remodeling of the extracellular matrix during development and growth of various tissues including the eye. Various functional polymorphisms in MMPs have been implicated in the pathogenesis of different types of glaucoma. The aim of the present study was to investigate the role of various polymorphisms in Pakistani patients with glaucoma. Methods: The present case-control study included 112 patients with primary open-angle glaucoma (POAG), 82 patients with primary angle closure glaucoma (PACG), and 118 control subjects. Genotyping of polymorphisms was done using PCR followed by restriction fragment length polymorphism analysis. Results: A signifcant difference in the genotype frequencies of MMP1 rs1799750 (-1607 1G/2G) was observed between the patients with POAG and the control subjects (p=0.001). This was attributed to the female subjects (p<0.001), while the association was not signifcant in male subjects (p>0.47). In addition, a signifcant difference was observed in genotype frequencies of MMP9 rs17576 (c.836A>G) in patients with PACG compared to the control subjects (p<0.001), which after gender stratifcation remained signifcant in men (p=0.009) but not in women (p=0.14). No signifcant associations were found for MMP7 (c.-181T>C) and MMP9 (c.-1562C>T) polymorphisms. Conclusions: Our data suggest that the MMP1 rs1799750 (-1607 1G/2G) and MMP9 rs17576 polymorphisms might be of value for further study as potential gender-dependent risk factors for developing POAG and PACG, respectively, in Pakistan. © 2013 Molecular Vision.

Micheal S.,Radboud University Nijmegen | Khan M.I.,Radboud University Nijmegen | Islam F.,Al Shifa Eye Trust Hospital | Akhtar F.,Al Shifa Eye Trust Hospital | And 6 more authors.
Cornea | Year: 2016

Background: Brittle cornea syndrome (BCS) is a rare autosomal recessive connective tissue disease characterized by variable combinations of corneal thinning and fragility, corneal ruptures either spontaneously or after minor trauma, blue sclerae, keratoconus, keratoglobus, and high myopia. So far, mutations in 2 genes, PRDM5 and ZNF469, have been associated with BCS. The purpose of this study is to describe novel mutations in the PRDM5 gene in patients with BCS. Methods and Results: Using homozygosity mapping with singlenucleotide polymorphism markers followed by whole-exome sequencing, we identified a novel homozygous splice site variant (c.93+5>A) in the PRDM5 gene in a consanguineous Pakistani family with 4 affected individuals. Reverse transcription-polymerase chain reaction analysis from lymphocyte-derived RNA failed to reveal any exon skipping because of this splice site variant. A homozygous variant (c.11>G; p.Gln4Pro) in SEC24D also segregated with the disease in this particular family. One previously known mutation (c.974del; p.Cys325LeufsX2) was identified in a sporadic patient with BCS from Serbia. Conclusions: The current study revealed a novel mutation in the PRDM5 gene in a BCS family and recurrent mutation in a sporadic BCS patient. A variant in the SEC24D gene also segregated in the BCS family, although its role in the disease remains unclear. © 2016 Wolters Kluwer Health, Inc. All rights reserved.

Micheal S.,Radboud University Nijmegen | Siddiqui S.N.,Al Shifa Eye Trust Hospital | Zafar S.N.,Al Shifa Eye Trust Hospital | Iqbal A.,University of Westminster | And 2 more authors.
PLoS ONE | Year: 2016

Background: Primary congenital glaucoma (PCG) is the most common form of glaucoma in children. PCG occurs due to the developmental defects in the trabecular meshwork and anterior chamber of the eye. The purpose of this study is to identify the causative genetic variants in three families with developmental and primary congenital glaucoma (PCG) with a recessive inheritance pattern. Methods: DNA samples were obtained from consanguineous families of Pakistani ancestry. The CYP1B1 gene was sequenced in the affected probands by conventional Sanger DNA sequencing. Whole exome sequencing (WES) was performed in DNA samples of four individuals belonging to three different CYP1B1-negative families. Variants identified by WES were validated by Sanger sequencing. Results: WES identified potentially causative novel mutations in the latent transforming growth factor beta binding protein 2 (LTBP2) gene in two PCG families. In the first family a novel missense mutation (c.4934G>A; p.Arg1645Glu) co-segregates with the disease phenotype, and in the second family a novel frameshift mutation (c.4031-4032insA; p.Asp1345Glyfs∗6) was identified. In a third family with developmental glaucoma a novel mutation (c.3496G>A; p. Gly1166Arg) was identified in the PXDN gene, which segregates with the disease. Conclusions: We identified three novel mutations in glaucoma families using WES; two in the LTBP2 gene and one in the PXDN gene. The results will not only enhance our current understanding of the genetic basis of glaucoma, but may also contribute to a better understanding of the diverse phenotypic consequences caused by mutations in these genes. © 2016 Micheal et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Micheal S.,COMSATS Institute of Information Technology | Micheal S.,Radboud University Nijmegen | Khan M.I.,COMSATS Institute of Information Technology | Khan M.I.,Radboud University Nijmegen | And 7 more authors.
Molecular Vision | Year: 2012

Purpose: To describe a novel mutation in the fibrillin-1 (FBN1) gene in a large Pakistani family with autosomal dominant Marfan syndrome (MFS). Methods: Blood samples were collected of 11 family members affected with Marfan syndrome, and DNA was isolated by phenol-extraction. The coding exons of FBN1 were analyzed by polymerase chain reaction (PCR) and direct sequencing. One hundred-thirty controls were screened for a mutation in the FBN1 gene that was identified in this family by restriction fragment length polymorphism (RFLP) analysis. Results: A novel heterozygous missense mutation c.2368T>A; p.Cys790Ser was observed in exon 19. This mutation substitutes a highly conserved cysteine residue by serine in a calcium binding epidermal growth factor-like domain (cbEGF) of FBN1. This mutation was present in all affected members and absent from unaffected individuals of the family in addition to 130 healthy Pakistani controls. Interestingly all affected family members presented with ectopia lentis, myopia and glaucoma, but lacked the cardinal cardiovascular features of MFS. Conclusions: This is a first report of a mutation in FBN1 in MFS patients of Pakistani origin. The identification of a FBN1 mutation in this family confirms the diagnosis of MFS patients and expands the worldwide spectrum of FBN1 mutations. © 2012 Molecular Vision.

Zafar A.V.,Military Hospital | Khan S.,Military Hospital | Zafar S.N.,Al Shifa Eye Trust Hospital
Journal of the College of Physicians and Surgeons Pakistan | Year: 2013

Objective: To determine the frequency of breast arterial calcifications (BAC) as seen on mammographic examination and to determine the association between BAC and hypertension, age, parity and weight of the person. Study Design: Cross-sectional analytic study. Place and Duration of Study: Department of Diagnostic Radiology, Military Hospital, Rawalpindi, from January 2006 to January 2007. Methodology: Two hundred patients undergoing mammography were studied to evaluate the association of BAC with raised blood pressure, age and parity. Previous history of lactation and the patients' weight were also recorded. Proportions of classes were compared using chi-square test. Results: 13.5% of the subjects (n = 200) were positive for BAC on mammograms. Mean age of the BAC positive subjects was higher than their counterparts found negative for BAC. Women bearing 5 - 6 children showed the highest frequency of BAC. Seventy seven (10.38%) of the BAC positive cases had previous history of lactation, whereas 15.44% (n = 123) had not breast fed their children and showed BAC. No significant association of presence of BAC was noted with the weight of the subjects. Conclusion: The frequency of presence of BAC on mammography was associated with systemic hypertension and higher age. It also increased with the reproductive parameters of a woman. © 2013 College of Physicians and Surgeons Pakistan.

Micheal S.,Radboud University Nijmegen | Ayub H.,Radboud University Nijmegen | Zafar S.N.,COMSATS Institute of Information Technology | Bakker B.,Radboud University Nijmegen | And 9 more authors.
Clinical and Experimental Ophthalmology | Year: 2015

Background: CYP1B1 is the most commonly mutated gene in primary congenital glaucoma (PCG), and mutations have also been identified in primary open-angle glaucoma (POAG). This study was undertaken to describe mutations in CYP1B1 in patients and families with PCG and POAG from Pakistan. Design: Case-control series. Participants: Forty families, 190 sporadic POAG cases and 140 controls from Pakistan. Methods: Patients and healthy individuals of one consanguineous Pakistani family were genotyped with high-resolution single nucleotide polymorphism microarrays. Homozygosity mapping was performed using HomozygosityMapper. Direct sequencing of CYP1B1 gene was performed in probands of the families, sporadic POAG cases and control individuals. Main Outcome Measures: Mutations in the CYP1B1 gene in PCG and POAG patients. Results: Homozygosity mapping in a consanguineous Pakistani family revealed one 11-Mb homozygous region encompassing the CYP1B1 gene. A homozygous CYP1B1 missense mutation (p.Arg390His) was identified in this family. Sequence analysis of CYP1B1 in 39 additional families revealed one known and three novel homozygous mutations in PCG (p.Ala288Pro, p.Asp242Ala, p.Arg355* and p.Arg290Profs*37). In POAG, one novel heterozygous missense mutation (p.Asp316Val) was identified in one family and a previously reported mutation (p.Glu229Lys) was identified in three families. Analysis of CYP1B1 in a panel of 190 sporadic POAG patients revealed three novel heterozygous variants (p.Thr234Lys, p.Ala287Pro and p.Gln362*) and three previously reported heterozygous variants (p.Gly61Glu, p.Glu229Lys and p.Arg368His). The p.Glu229Lys variant was significantly associated with POAG (P=0.03; odds ratio 2.49). Conclusions: This study confirms that CYP1B1 mutations are associated with POAG and PCG in the Pakistani population. © 2014 Royal Australian and New Zealand College of Ophthalmologists.

Micheal S.,COMSATS Institute of Information Technology | Micheal S.,Radboud University Nijmegen | Khan M.I.,COMSATS Institute of Information Technology | Khan M.I.,Radboud University Nijmegen | And 5 more authors.
Molecular Vision | Year: 2012

Purpose: Single nucleotide polymorphisms (SNPs) rs1048661 (p.R141L) and rs3825942 (p.G153D) in the lysyl oxidaselike 1 (LOXL1) gene have been previously reported to be associated with pseudoexfoliation glaucoma (PEXG) in various Asian and European populations, but these SNPs have not yet been studied in the Pakistani population. Therefore the aim of the present study was to investigate the association of these two coding LOXL1 SNPs in Pakistani PEXG patients. Methods: One hundred twenty-eight Pakistani patients diagnosed with PEXG and 180 healthy controls were recruited for the study. Genomic DNA was extracted and both SNPs were genotyped by direct sequencing. Association of genotype and allele frequencies with PEXG were analyzed using the Chi-square (χ2) test. Results: Genotype and allele frequencies of both rs1048661 and rs3825942 were found to be significantly associated with PEXG. The GG genotypes of both LOXL1 SNPs were associated with an increased risk of developing PEXG. In addition the G alleles of rs1048661 and rs3825942 confer an increased risk for PEXG with an odds ratio (OR) of 2.98 (95% CI 1.94-4.57) and OR 6.83 (95% CI 2.94-16.67), respectively. Conclusions: A significant association was found for the G allele of rs1048661 and rs3825942 in PEXG patients of Pakistani origin. © 2012 Molecular Vision.

Yousaf S.,COMSATS Institute of Information Technology | Khan M.I.,COMSATS Institute of Information Technology | Micheal S.,COMSATS Institute of Information Technology | Akhtar F.,Al Shifa Eye Trust Hospital | And 8 more authors.
Molecular Vision | Year: 2011

Purpose: The present study was designed to determine the association of polymorphisms of the DNA repair genes X-ray cross-complementing group 1 (XRCC1) (c.1316G>A [rs25487]) and xeroderma pigmentosum complementation group D (XPD) (c.2298A>C [rs13181]) with primary open-angle glaucoma (POAG) and primary closed-angle glaucoma (PCAG). Methods: In this prospective case-control study, polymerase chain reaction-restriction fragment length polymorphism analysis was used to study the association of XRCC1 and XPD with 160 POAG patients, 163 PCAG patients, and 193 unaffected controls. Results: XRCC1 rs25487 was found to be significantly associated specifically with male POAG patients (χ2=13.2 [p=0.001]), only for the dominant model (odds ratio [OR]=2.65 [95% confidence interval [CI]=1.44-4.85], p<0.005). In addition XPD rs13181 was also found to be associated with male POAG patients (χ2=12.1 [p<0.005]), for both dominant (OR=2.44 [95% CI=1.33-4.47], p<0.005) as well as recessive model (OR=3.62 [95% CI=1.45-9.01], p<0.01). Combined genotypes of both the genes revealed that the heterozygote AC/GA was significantly associated with the male POAG patients (z=3.00 [p<0.001]). The AA/GG genotype was present at a higher frequency in the male controls and the AA/ GA in the female controls and could thus have a protective role in males and females, respectively. Conclusions: We postulate that defects in the DNA repair genes XRCC1 and XPD may possibly be associated with the progression of POAG in male patients of Pakistani origin. © 2011 Molecular Vision.

Nazullah,Khyber Teaching Hospital | Shah A.,Al Shifa Eye Trust Hospital | Ahmed M.,Hayatabad Medical Complex | Baseer A.,Khyber Teaching Hospital | And 2 more authors.
Journal of Medical Sciences | Year: 2010

Objectives: The main objective of this study was to compare the recurrence rate of pterygium after excision using bare sclera technique and free conjunctival autograft (CAG). Material & Methods: This was a comparative interventional case series conducted from March 2005 to March 2006 in the Ophthalmology Department of Khyber Teaching Hospital Peshawar. A total of 60 patients were included in this study. The patients were divided into. Group A and group B. An equal number of patients were included in each group. We used the bare sclera technique for group A patients and free conjunctival autograft (CAG) for group B. In free conjunctival autograft (CAG), the bare sclera was measured with a caliper and a graft of the same size was taken from the supero temporal region of the bulbar conjunctiva and grafted onto the bare sclera suturing it with 10/0 nylon to the surrounding conjunctiva. All patients were operated under subconjunctival anesthesia. Results: Out of 60 patients, 67% were male and 33% female. Patient age ranged from 20-50 years. The recurrence was 36.6% in group A and 6.6% in group B. Conclusion: Free conjunctival autograft is a better technique for prevention of recurrence after pterygium surgery.

PubMed | Sudan University of Science and Technology, Sustainable Development Technology, Al Shifa Eye Trust Hospital, Bahauddin Zakariya University and 2 more.
Type: Journal Article | Journal: PloS one | Year: 2015

Homozygosity mapping has facilitated the identification of the genetic causes underlying inherited diseases, particularly in consanguineous families with multiple affected individuals. This knowledge has also resulted in a mutation dataset that can be used in a cost and time effective manner to screen frequent population-specific genetic variations associated with diseases such as inherited retinal disease (IRD).We genetically screened 13 families from a cohort of 81 Pakistani IRD families diagnosed with Leber congenital amaurosis (LCA), retinitis pigmentosa (RP), congenital stationary night blindness (CSNB), or cone dystrophy (CD). We employed genome-wide single nucleotide polymorphism (SNP) array analysis to identify homozygous regions shared by affected individuals and performed Sanger sequencing of IRD-associated genes located in the sizeable homozygous regions. In addition, based on population specific mutation data we performed targeted Sanger sequencing (TSS) of frequent variants in AIPL1, CEP290, CRB1, GUCY2D, LCA5, RPGRIP1 and TULP1, in probands from 28 LCA families.Homozygosity mapping and Sanger sequencing of IRD-associated genes revealed the underlying mutations in 10 families. TSS revealed causative variants in three families. In these 13 families four novel mutations were identified in CNGA1, CNGB1, GUCY2D, and RPGRIP1.Homozygosity mapping and TSS revealed the underlying genetic cause in 13 IRD families, which is useful for genetic counseling as well as therapeutic interventions that are likely to become available in the near future.

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