p.R138Q and p.R229Q Screening In NPHS2 Gene in a Moroccan Cohort with Steroid Resistant Nephrotic Syndrome

Mutations in the NPHS2 gene encoding podocin are implicated in an autosomal-recessive form of nonsyndromic steroid-resistant nephrotic syndrome in both pediatric and adult patients. The p.R138Q (c.413G>A) mutation in exon 3 was the most prevalent mutation in European series. The p.R229Q (c.686G>A) variant in exon 5 is the first human variant discovered with a mutation-dependent pathogenicity. We aimed in this study to screen for the p.R138Q mutation and the p.R138Q variant in a Moroccan cohort with Steroid Resistant Nephrotic Syndrome.

NPHS2 gene polymorphism aggravates renal damage caused by focal segmental glomerulosclerosis with COL4A3 mutation

Focal segmental glomerulosclerosis (FSGS), a type of primary glomerular disease, is the leading cause of end-stage renal disease (ESRD). Several studies have revealed that certain single-gene mutations are involved in the pathogenesis of FSGS; however, the main cause of FSGS has not been fully elucidated. Homozygous mutations in the glomerular basement membrane gene can lead to early renal failure, while heterozygous carriers develop renal failure symptoms late. Here, molecular genetic analysis of clinical information collected from clinical reports and medical records was performed. Results revealed that nephrosis 2 (NPHS2) gene polymorphism aggravated renal damage in three FSGS families with heterozygous COL4A3 mutation, leading to early renal failure in index patients. Our findings suggest that COL4A3 and NPHS2 may have a synergistic effect on renal injury caused by FSGS. Further analysis of the glomerular filtration barrier could help assess the cause of kidney damage. Moreover, a detailed analysis of the glomerular basement membrane-related genes and podocyte structural proteins may help us better understand FSGS pathogenesis and provide insights into the prognosis and treatment of hereditary glomerulonephropathy.

Relation between Single Nucleotide Polymorphism rs3738423 (C>T) of NPHS2 Gene and some Biochemical Parameters in Pediatrics Nephrotic Syndrome Patients

Clinical biochemical parameters were known as important criteria for diagnosis and treatment of nephrotic syndrome (NS). Single nucleotide polymorphism (SNP) rs3738423 (C>T) of NPHS2 gene encoding for podocin protein in globular membrane was proved associated to steroid resistant nephrotic syndrome. This study was to evaluate the relation between rs3738423 (C>T) of NPHS2 gene and biochemical parameters of pediatrics NS patients in steroid- sensitive (SS), early (ESR) and late (LSR) steroid resistant groups. Blood and urine samples from 149 patients were collected for protein, albumin and protein/creatinine analysis; blood samples in EDTA tube were used for NPHS2 gene analysis. The results showed that CC and CT genotypes were mostly abundant in all three groups, whereas TT was minor appeared in only SS and KTM groups. Patients with the CT genotypes in the ESR group had a protein/creatinine index nearly twice as high as those patients with the CC genotypes. Meanwhile, those with CT genotypes in the SS and LSR groups had lower rates than the CC genotypes. Clinical biochemical parameters significantly contributed to the diagnosis, monitoring and treatment of pediatrics nephrotic syndrome, the changes of these parameters depended on the interaction between the response to corticoid and rs3738423 (C>T) polymorphism of NPHS2 gene in pediatrics nephrotic syndrome patients.

First Report of Preimplantation Genetic Diagnosis for Steroid-Resistant Nephrotic Syndrome

Background: Steroid-resistant nephrotic syndrome is a genetic disease with autosomal recessive inheritance pattern and symptoms such as proteinuria and hypoalbuminemia and rapid progress of kidney disease. Preimplantation genetic diagnosis is an option for couples who are at risk of affected pregnancy to have a healthy child. Objectives: This study aimed to develop a new PGD test for a couple who are heterozygous for a mutation in NPHS2 gene and have a son affected to steroid-resistant nephrotic syndrome. Methods: Variant detection by cycle sequencing and Multiplex fluorescent PCR for identification of flanking STR markers were used to investigate the status of the embryos. Results: Three out of six embryos were transferable from which one was transferred and resulted in the birth of a healthy boy. Conclusions: We recommend increasing the number of the STR markers to two at the downstream of the NPHS2 gene especially in cases that direct mutation analysis such as cycle sequencing is not applied.