Genetic mutation in Egyptian children with steroid-resistant nephrotic syndrome

Thomas, Manal M.; Abdel‐Hamid, Mohamed S.; Mahfouz, Nermine N.; Ghobrial, Emad E.

doi:10.1016/j.jfma.2017.02.012

Cited by 12 publications

(10 citation statements)

References 24 publications

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“…Moreover, our study results were interestingly in keeping with the national study done in the Pediatric Nephrology Clinic, Cairo University Children's Hospital and Genetics Department, National Research Centre (2017). They did not discover mutation of p.R229Q in exon 5 among Egyptian children (18) .…”

Section: Discussionmentioning

confidence: 92%

Association of Mutations in The NPHS2 Gene and Nephrotic Syndrome in Children and Adults in Middle East

Tony¹,

Aboushall

Alwaheeb³

et al. 2022

The Egyptian Journal of Hospital Medicine

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Background: Limited and contradictory pharmacogenetic studies of NPHS2 gene R229Q polymorphism in nephrotic syndrome (NS) children and adults of different ethnicities steered us to investigate the genotype frequency and associated risk of this polymorphism in Middle East NS children and adults. Objectives: The present work aimed to study the effect of NPHS2 R229Q genetic variations on the susceptibility to idiopathic NS and the treatment response in NS children and adults from Assiut University and major Kuwait Hospitals. Patients and methods: A prospective observational cohort study was conducted which comprised a total of 100 idiopathic NS patients (30 children and 70 adults). Mutation analysis was carried out by Taqman allele discrimination of the NPHS2 gene R229Q polymorphism (rs61747728) using specific primers and probes. Results:The results indicate the presence of R229Q polymorphism in 9% of our patients. Moreover, R229Q variant in Steroid-resistant nephrotic syndrome (SRNS) adults was observed in a single heterozygous form. A total of 100 patients were genotyped for the variant rs61747728. Ninety-one percent of patients carry the CC genotype (Homozygous), in addition only 9% were carriers of the CT genotype (Heterozygous), whereas no patients were carrying the TT genotype. The minor allele (T) frequency was 0.045, whereas the major allele (C) frequency was 0.955 in our population. Conclusion: NPHS2 p.R229Q plays an important role in enhancing the susceptibility of minimal change disease (MCD), focal segmental glomerulosclerosis/steroid-resistant nephrotic syndrome (FSGS/SRNS), especially in Middle East population and age of late-onset patients. We recommend to screen for p.R229Q polymorphism in the diagnosis of SRNS among our population.

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Section: Discussionmentioning

confidence: 92%

Association of Mutations in The NPHS2 Gene and Nephrotic Syndrome in Children and Adults in Middle East

Tony¹,

Aboushall

Alwaheeb³

et al. 2022

The Egyptian Journal of Hospital Medicine

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“…Different genetic mutations in different populations make the need for genetic testing and histological pattern determination of different populations valuable for disease prognosis and management. There have been previous studies screening for NPHS2 mutations in the Egyptian population that showed novel mutations [51,52]. Therefore, in this study we looked for new mutations of the PLCE1 gene in Egyptian SRNS patients.…”

Section: Discussionmentioning

confidence: 99%

Mutational analysis of phospholipase C epsilon 1 gene in Egyptian children with steroid-resistant nephrotic syndrome

Abdou

Ramadan

El-Agamy

et al. 2022

Egypt J Med Hum Genet

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Background Steroid-resistant nephrotic syndrome (SRNS) is characterized by unresponsiveness of nephrotic range proteinuria to standard steroid therapy, and is the main cause of childhood renal failure. The identification of more than 53 monogenic causes of SRNS has led researchers to focus on the genetic mutations related to the molecular mechanisms of the disease. Mutations in the PLCE1 gene, which encodes phospholipase C epsilon 1 (PLCε1), have been described in patients with early-onset SRNS characterized by progressive renal failure. In this study we screened for PLCE1 mutations in Egyptian children with SRNS. This is a descriptive case series study aiming to screen for PLCE1 gene mutations by direct sequencing of five exons—9, 12, 15, 19, 27—in 20 Egyptian children with SRNS who entered the Nephrology Unit, Faculty of Medicine, Ain-Shams University from November 2015 to December 2017. The variants detected were submitted to in silico analysis. Results We screened for mutations in five selected exons of PLCE1 gene. We identified seven variants in the five selected exons with homozygous and heterozygous inheritance pattern, two are intronic variants, two are silent variants, and three are missense variants. We identified four novel variants two are silent with no clinical significance and two are missense with uncertain clinical significance and pathogenic in-silico predictions; one p.Arg1230His in exon 12, the other is p.Glu1393Lys in exon 15. Conclusions We identified four novel mutations, findings which added to the registered SNP spectrum of the PLCE1 gene. These results widen the spectrum of PLCE1 gene mutations and support the importance of genetic testing in different populations of SRNS patients, therefore, to assess the vulnerability of Egyptian children to SRNS candidate genes, further studies needed on a larger number of cases which undoubtedly provide new insights into the pathogenic mechanisms of SRNS and might help in control of the patient. Additionally, the use of computational scoring and modeling tools may assist in the evaluation of the way in which the SNPs affect protein functionality.

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“…NPHS2 mutations first found in early-onset autosomal recessive familial and sporadic SRNS (44). NPHS2 gene harbors 8 exons and encodes podocin, an interrelated protein with nephrin.…”

Section: Podocinmentioning

confidence: 99%

The importance of genetic study in steroid-resistant nephrotic syndrome

et al. 2019

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Steroid-resistant nephrotic syndrome (SRNS) is a challenging clinical task. It has heterogeneous etiology and extremely variable clinical outcomes and generally progresses to end-stage renal disease (ESRD). Different gene mutations in podocyte’s slit diaphragm, mitochondria, and cytoskeleton proteins, as well as glomerular basement membrane (GBM) have been associated with SRNS. These proteins regulate the function of the glomerular filtration barrier. Advances in genetic approaches and podocytology have led to discover the SRNS-causing genes that lead to a better understanding of the drug resistance. More than 45 genetic mutations have been recognized in the hereditary form of SRNS. This review offers an update on the current knowledge of steroid resistance-causing gene mutations in podocytes. Understanding the specific genes involved in SRNS would guarantee an optimum therapeutic benefit of steroid treatment.

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Genetic mutation in Egyptian children with steroid-resistant nephrotic syndrome

Cited by 12 publications

References 24 publications

Association of Mutations in The NPHS2 Gene and Nephrotic Syndrome in Children and Adults in Middle East

Association of Mutations in The NPHS2 Gene and Nephrotic Syndrome in Children and Adults in Middle East

Mutational analysis of phospholipase C epsilon 1 gene in Egyptian children with steroid-resistant nephrotic syndrome

The importance of genetic study in steroid-resistant nephrotic syndrome

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