الفهرس 
IntroductionOnly 14 pages are availabe for public view
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Abstract
Nephrotic syndrome (NS) is regarded as the most common childhood kidney disorder in which the permeability and selectivity of the glomerular filtration barrier are altered, resulting in the leakage of a high amount of blood proteins. The main treatment strategy for nephrotic syndrome children patients is the admission of steroid therapy. While most patients respond well to the steroid therapy and are called steroid sensitive, however, 20 % of children patients are resistant to therapy.
Steroid-resistant nephrotic syndrome (SRNS) is characterized by resistance 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. The current study has 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 putative 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. This study identified seven variants in the five selected exons with homozygous and heterozygous inheritance patterns, two are intronic variants, two are silent variants, and three are missense variants. The current study 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.
These four novel mutations added to the registered SNP spectrum of the PLCE1 gene. These results support the idea of the importance of genetic screening for different ethnic groups in disease genotyping, and for early diagnosis.
The use of computational scoring and modeling tools may assist in the evaluation of how the SNPs affect protein functionality, and their linkage to clinical phenotype.