<i>NPHS2</i>Mutations: A Closer Look to Latin American Countries

Guaragna, Mara Sanches; Lutaif, Anna Cristina G.B.; Maciel‐Guerra, Andréa T.; Belangero, Vera Maria Santoro; Guerra‐Júnior, Gil; Mello, Maricilda Palandi de

doi:10.1155/2017/7518789

Cited by 6 publications

(10 citation statements)

References 54 publications

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“…Therefore, genetic testing aids the clinicians to guide the pharmacological treatment avoiding exposure to drugs that would only contribute to unnecessary toxicity and consider the renal transplant in those patients with a genetic origin of steroid-resistant nephrotic syndrome (SRNS) (28,29). Nonetheless, scarce data is available about the prevalence of NPHS2 mutations in pediatric Latin American patients (30). In our study, no pathogenic variants in NPHS2 were found and most of the observed polymorphisms were previously reported and classified as benign.…”

Section: Discussionmentioning

confidence: 99%

Administration of enteric-coated mycophenolate sodium in children with steroid-resistant nephrotic syndrome and focal segmental glomerulosclerosis

Caletti¹,

Ibañez²,

Guido³

et al. 2017

J Nephropathol

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Background: Pediatric patients with steroid-resistant nephrotic syndrome (SRNS) and focal segmental glomerulosclerosis (FSGS) may relapse and current second line agents include mycophenolate mofetil. However, there is no current information about the use of the sodium salt of mycophenolic acid (SMPA) in this population. Objectives: We conducted a prospective study on the efficacy and pharmacokinetics of SMPA in children with FSGS. Patients and Methods: Patients without NPHS2 pathogenic variants received SMPA at dosages between 460 to 720 mg/m2/d for 12 months after previous treatments failure. Clinical and biochemical assessments were performed. Blood samples were obtained after the first dose and at steady state (3 months after the onset of treatment) and total and free mycophenolic acid (MPA) was quantitated using HPLC-UV. Results: Two patients showed partial remission after the 12-month period of SMPA treatment with a notable decrease in proteinuria and an increase in serum albumin levels. Maximum MPA concentrations after the first dose and at steady state were 11.6 µg/mL and 10.5 µg/mL, respectively, without drug accumulation. Maximum MPA free levels after the first dose and at steady state were 192.9 and 120.6 ng/mL, respectively. MPA levels became undetectable after 4 hours of the administration in all cases. Conclusions: SMPA is a promising agent for pediatric patients with SRNS and FSGS but SMPA schedule of treatment should be revised with shorter intervals of administration and higher doses than those used in the present study in order to attain higher systemic exposures and accumulation of the immunosuppressant drug. Further efficacy and pharmacokinetic studies should be performed to confirm these findings.

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Section: Discussionmentioning

confidence: 99%

Administration of enteric-coated mycophenolate sodium in children with steroid-resistant nephrotic syndrome and focal segmental glomerulosclerosis

Caletti¹,

Ibañez²,

Guido³

et al. 2017

J Nephropathol

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“…NPHS2 gene harbors 8 exons and encodes podocin, an interrelated protein with nephrin. Some mutations in the coding sequence of gene may alter its structure and stability and thus, disrupt its functional association and cause proteinuria (45). NPHS2 mutations are associated with infantile-onset, SRNS accompanied by FSGS, and progression to renal failure.…”

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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“…Previous studies claim that incidence of NPHS2 mutations in children may vary according to ethnicity (Thomas et al 2018;Guaragna et al 2017). In 2013 Basiratnia et al (Basiratnia et al 2013) showed that NPHS2 mutations were about 31%, responsible for 57% and 26% of sporadic and familial forms of SRNS.…”

Section: Whole Exome Sequencing (Wes)mentioning

confidence: 99%

Molecular genetic analysis of Steroid Resistant Nephrotic Syndrome: Detection of a novel mutation

Serajpour

Karimi

Hooman

et al. 2018

Preprint

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Background: Nephrotic syndrome is one of the most common kidney diseases in childhood. About 20% of children are steroid-resistant NS (SRNS) which progress to end-stage renal disease (ESRD). More than 53 genes are associated with SRNS which represent the genetic heterogeneity of SRNS. This study was aimed to screen disease causing mutations within NPHS1 and NPHS2 and evaluate new potential variants in other genes.Method: In first phase of study, 25 patients with SRNS were analyzed for NPHS1 (exon 2, 26) and all exons of NPHS2 genes by Sanger sequencing. In the second phase, whole exome sequencing was performed on 10 patients with no mutations in NPHS1 and NPHS2.Result: WES analysis revealed a novel mutation in FAT1 (c.10570C>A; Q3524K). We identified 4 pathogenic mutations, located in exon 4 and 5 of NPHS2 gene in 20% of patients (V180M, P118L, R168C and Leu156Phe). Also our study has contributed to the descriptions of previously known pathogenic mutations across WT1 (R205C) and SMARCAL1 (R764Q) and a novel polymorphism in CRB2.Conclusion: Our study concludes that mutations of exon 4 and 5 NPHS2 gene are common in Iranian and some other ethnic groups. We suggest conducting WES after NPHS2 screening and further comprehensive studies to identify the most common genes in the development of SRNS, which might help in Clinical impact on management in patients with SRNS.All rights reserved. No reuse allowed without permission.(which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint . http://dx

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NPHS2Mutations: A Closer Look to Latin American Countries

Cited by 6 publications

References 54 publications

Administration of enteric-coated mycophenolate sodium in children with steroid-resistant nephrotic syndrome and focal segmental glomerulosclerosis

Administration of enteric-coated mycophenolate sodium in children with steroid-resistant nephrotic syndrome and focal segmental glomerulosclerosis

The importance of genetic study in steroid-resistant nephrotic syndrome

Molecular genetic analysis of Steroid Resistant Nephrotic Syndrome: Detection of a novel mutation

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