Dataset Information

Analysis of NPHS2 Gene Mutations in Egyptian Children with Nephrotic Syndrome.

ABSTRACT: BACKGROUND:Mutations in the NPHS2 genes are the main aetiology of early-onset and familial steroid-resistant nephrotic syndrome (SRNS). The pathogenic NPHS2 mutation together with the p.R229Q variant has been less described among Egyptian children. AIM:This study aims to determine the mutation of NPHS2 in children with NS and discover the role of p.R229Q variant in SRNS. METHODS:The study included 53 children with NS, and 53 healthy volunteers matched in age and sex controls. The median age at disease onset was 7.3 years. Among NS cases, 31 cases had steroid-sensitive nephrotic syndrome (SSNS) and 22 children with steroid-resistant nephrotic syndrome (SRNS). Polymerase chain reaction amplification of the whole coding region of NPHS2 gene was carried out for its mutational analysis. Restriction digestion testing was carried out after PCR to determine the presence of R229Q polymorphism. Randomly selected samples were re-genotyped by two independent technicians for assessment of Quality control. RESULTS:NS patients showed a significant higher frequency of heterozygous genotype GA (89.5%) compared to control group (10.5%) with increased risk of NS (OR, 12.04; 95% CI, 2.61 to55.38; p < 0.0001). Moreover, SRNS showed a significant higher frequency of GA genotype (68.2%) than the SSNS group (6.5%). The GA genotype was associated with increased risk of SRNS (OR, 31.1; 95% CI, 5.73 to 168.48; P < 0.001) and the A allele was associated with increased risk of SRNS (OR, 15.52; 95% CI, 3.325 to 72.422; P < .001). CONCLUSION:R229Q polymorphisms are associated with SRNS, and any child with SRNS should be searched for mutations in the NPHS2 gene.

SUBMITTER: Zaki M

PROVIDER: S-EPMC6953933 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Publications

Analysis of <i>NPHS2</i> Gene Mutations in Egyptian Children with Nephrotic Syndrome.

Zaki Moushira M El-Shaer Shreen S Rady Sahar S El-Salam Manal Abd MA Abd-El-Salam Ragaa R Alkashlan Ibrahim Abdelfattah IA Saber Mohamed M Mohamed Sanaa S Hassaan Mohamed M Rabie Eman E Amr Khalda K

Open access Macedonian journal of medical sciences 20191009 19

<h4>Background</h4>Mutations in the <i>NPHS2</i> genes are the main aetiology of early-onset and familial steroid-resistant nephrotic syndrome (SRNS). The pathogenic <i>NPHS2</i> mutation together with the p.R229Q variant has been less described among Egyptian children.<h4>Aim</h4>This study aims to determine the mutation of <i>NPHS2</i> in children with NS and discover the role of p.R229Q variant in SRNS.<h4>Methods</h4>The study included 53 children with NS, and 53 healthy volunteers matched i ...[more]

PMID: 31949506

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Project description:BACKGROUND: Nephrotic syndrome is traditionally classified on the basis of the response to standard steroid treatment. Mutations in more than 24 genes have been associated with nephrotic syndrome in children, although the great majority of steroid-resistant cases have been attributed to mutations in three main genes: NPHS1, NPHS2 and WT1. The aims of this study were to identify mutations in these genes more frequently reported as mutated and to characterize each variation using different in silico prediction algorithms in order to understand their biological functions. METHODS: We performed direct sequence analysis of exons 8 and 9 of WT1, 8 exons of NPHS2 and 29 exons of NPHS1, including NPHS2 and NPHS1 intron-exon boundary sequences, as well as 700 bp of the 5' UTR from both genes in 27 steroid-resistant patients aged between 3 months and 18 years. RESULTS: Analysis of the NPHS2 gene revealed four missense mutations, one frameshift mutation and three variations in the 5' UTR. Four patients presented compound heterozygosis, and four other patients presented one heterozygous alteration only. WT1 and NPHS1 gene analysis did not reveal any mutations. DISCUSSION: This is the first study focusing on genetics of SRNS in Brazilian children. Identification of mutations is important because it could influence physicians' decision on patient treatment, as patients carrying mutations can be spared the side effects of immunosuppressive therapy and ultimately could be considered for kidney transplantation from a living donor. CONCLUSIONS: After molecular analysis of the genes more frequently reported as mutated in 27 steroid-resistant nephrotic syndrome patients, we identified NPHS2 mutations confirming the hereditary character of the kidney disease in only 14.8% of patients. Therefore, the next step is to perform a next generation sequencing based analysis of glomeluropathy-related panel of genes for the remaining patients in order to search for mutations in other genes related to steroid-resistant nephrotic syndrome.

Dataset Information

Analysis of NPHS2 Gene Mutations in Egyptian Children with Nephrotic Syndrome.

Publications

Analysis of <i>NPHS2</i> Gene Mutations in Egyptian Children with Nephrotic Syndrome.

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