The novel heterozygous Thr377Arg MYOC mutation causes severe Juvenile Open Angle Glaucoma in a large Pakistani family

Waryah, Ali Muhammad; Narsani, Ashok Kumar; Sheikh, Shakeel A.; Shaikh, Hina; Shahani, Muhammad Yaqoob

doi:10.1016/j.gene.2013.07.016

Cited by 22 publications

(16 citation statements)

References 20 publications

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“…Genomic DNA was extracted from the whole blood by salting out method [Waryah et al, 2013] . Primer sequences and PCR thermal profiles were used for the amplification of three IL28B Snps (rs12979860, rs8099917, and rs12980275) as reported by [Venegas et al, 2011;El-Awady et al, 2012;Sharafi et al, 2012].…”

Section: Il28b Genotypingmentioning

confidence: 99%

IL28Brs12980275 polymorphism shows association with response to treatment in Pakistani patients with Chronic Hepatitis C

Waryah

Devrajani

et al. 2015

J. Med. Virol.

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The aim of this study was to describe the genetic characteristics of Pakistani patients infected with hepatitis C virus (HCV) in relation to IL28B polymorphisms and its association to interferon and ribavirin treatment response. A total of 220 patients, infected with HCV were enrolled, out of which 100 were responders and 120 were nonresponders. The whole blood samples were collected to extract viral RNA and genomic DNA. PCR following the restriction fragment length polymorphism method was used to genotype IL28B rs12979860, rs8099917, and rs12980275 polymorphisms. Liver biopsies and HCV genotyping were performed in nonresponder patients. The rs12980275 AA genotype exhibited significant correlation to treatment response and was found in 62% of the responders and 37.5% of nonresponder patients, whereas AG genotype was noticed frequently in the nonresponder group (P < 0.0001). The rs12979860 CT and rs8099917 TT genotypes were found in 74% and 66% of the responders as compared to 58.3% and 50.8% in nonresponder patients (P = 0.001 and P = 0.032) respectively. HCV 3a genotypes were detected in 50.8% of the nonresponder patients. No significant association was detected between liver biopsy findings and IL28B SNPs (P > 0.05). The results showed the significant association of rs12980275 polymorphism with treatment response in HCV patients followed by rs12979860 and rs8099917. This is the first report describing the association of rs12980275 with response to HCV treatment from Pakistan. These findings may help in predicting the outcome of pegylated interferon and ribavirin treatment in HCV patients, and may reduce the side effects and cost of treatment in predicting non-responder patients.

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Section: Il28b Genotypingmentioning

confidence: 99%

IL28Brs12980275 polymorphism shows association with response to treatment in Pakistani patients with Chronic Hepatitis C

Waryah

Devrajani

et al. 2015

J. Med. Virol.

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“…First described MYOC correlated glaucoma from Pakistan isolating as autosomal dominant peculiarity in large family detected with JOAG (Waryah et al, 2013 …”

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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“…3 The study of consanguineous families has facilitated the discovery of pathogenic genetic variants in many autosomal recessive disorders. [4][5][6] The frequency of autosomal recessive disorders is higher in populations where consanguineous marriages are frequent. 7 Consanguinity results in higher risk for birth defects varying from 2.7% to 15.8%.…”

Section: Introductionmentioning

confidence: 99%

Biallelic variants in LINGO1 are associated with autosomal recessive intellectual disability, microcephaly, speech and motor delay

Ansar

Riazuddin

Sarwar

et al. 2018

Genetics in Medicine

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Purpose: To elucidate the novel molecular cause in two unrelated consanguineous families with autosomal recessive intellectual disability.Methods: A combination of homozygosity mapping and exome sequencing was used to locate the plausible genetic defect in family F162, while only exome sequencing was followed in the family PKMR65. The protein 3D structure was visualized with the University of California-San Francisco Chimera software.Results: All five patients from both families presented with severe intellectual disability, aggressive behavior, and speech and motor delay. Four of the five patients had microcephaly. We identified homozygous missense variants in LINGO1, p.(Arg290His) in family F162 and p.(Tyr288Cys) in family PKMR65. Both variants were predicted to be pathogenic, and segregated with the phenotype in the respective families. Molecular modeling of LINGO1 suggests that both variants interfere with the glycosylation of the protein.Conclusion: LINGO1 is a transmembrane receptor, predominantly found in the central nervous system. Published loss-offunction studies in mouse and zebrafish have established a crucial role of LINGO1 in normal neuronal development and central nervous system myelination by negatively regulating oligodendrocyte differentiation and neuronal survival. Taken together, our results indicate that biallelic LINGO1 missense variants cause autosomal recessive intellectual disability in humans.

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The novel heterozygous Thr377Arg MYOC mutation causes severe Juvenile Open Angle Glaucoma in a large Pakistani family

Cited by 22 publications

References 20 publications

IL28Brs12980275 polymorphism shows association with response to treatment in Pakistani patients with Chronic Hepatitis C

IL28Brs12980275 polymorphism shows association with response to treatment in Pakistani patients with Chronic Hepatitis C

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

Biallelic variants in LINGO1 are associated with autosomal recessive intellectual disability, microcephaly, speech and motor delay

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