NPHS2 mutations account for only 15 % of nephrotic syndrome cases

Guaragna, Mara Sanches; Lutaif, Anna Cristina G.B.; Piveta, Cristiane S C; Souza, Marcela Lopes de; Souza, Suéllen Rodrigues De; Henriques, Taciane Barbosa; Maciel‐Guerra, Andréa T.; Belangero, Vera Maria Santoro; Guerra, Gil; Mello, Maricilda Palandi de

doi:10.1186/s12881-015-0231-9

Cited by 22 publications

(16 citation statements)

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“…a study which was carried out in northwest of Iran by Behbahan et al (Behbahan et al 2013) in 2013 reveled 6 different mutations in 80% of SRNS children showed no mutation within these exons. Similar to Brazilian (Guaragna et al 2015) and polish (Binczak-Kuleta et al 2014) studies, our result indicated pathogenic mutation neither within these exons among all patients nor in other exons of the cases studied by WES. Due to Behbahan's findings (Behbahan et al 2013) and our study, we suppose that exon 2 and 26 of NPHS1 gene may not be as causative exons for SRNS in Iranian children.…”

Section: Whole Exome Sequencing (Wes)supporting

confidence: 89%

“…( 0.058, 0.671,_) ( Table.3) . NPHS2 mutations have been reported as the most common cause of childhood onset in autosomal recessive SRNS (Sadowski et al 2015;Guaragna et al 2015;Tasic et al 2015). The most frequent renal histological feature Associated with SRNS is focal segmental glomerulosclerosis (FSGS) (Joshi et al 2013;Liu and Wang 2017).…”

Section: Whole Exome Sequencing (Wes)mentioning

confidence: 99%

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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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Section: Whole Exome Sequencing (Wes)supporting

confidence: 89%

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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“…In a small Brazilian study 27 steroid-resistant nephrotic syndrome patients wete tested for mutations in NPHS1, NPHS2 and WT1 gene [19]. Only mutations in NPHS2 were detected confirming the hereditary character of the kidney disease in only 14.8% of patients.…”

Section: Other Studiesmentioning

confidence: 92%

Steroid Resistant Nephrotic Syndrome-Genetic Consideration

Tasić

Gucev

Polenakovič

2015

Prilozi

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Nephrotic syndrome is defined as the association of massive proteinuria, hypoalbuminaemia, edema, and hyperlipidemia. It is separated to steroid-sensitive or steroid-resistant (SRNS) forms in respect to the response to intensive steroid therapy. SRNS usually progresses to end-stage renal failure. According to the North American Pediatric Renal Trials and Collaborative Studies SRNS constitutes the second most frequent cause of ESRD in the first two decades of life. Unfortunately, there is no curative treatment for majority of patients. Majority of the SRNS patients have the histologic picture of focal segmental glomerulosclerosis. Interestingly, the risk of recurrence in the kidney graft in patients with hereditary SRNS is lower than in those who do not have genetic background. The etiology and pathogenesis of SRSN has remained enigma for decades. The discovery of 39 dominant or recessive SRNS genes enabled better understanding of the function of the glomerular podocytes and slit membrane. Hildebrandt's group has shown that 85% of the SRNS cases with onset by 3 months of age and 66% with onset by 1 year of age can be explained by recessive mutations in one of four genes only (NPHS1, NPHS2, LAMB2, or WT1). The same group used modern diagnostic techniques such as the next generation sequencing and tested a large international cohort of SRNS patients (n = 1783 families). The diagnostic panel included 21 genes with a recessive mode of inheritance and 6 genes with a dominant mode of inheritance. Single-gene cause was detected in 29.5% (526 of 1783) of the families with SRNS that manifested before 25 years of age. The identification of causative single-gene mutations may have important therapeutic consequences in some cases. This is very important for patients who carry mutations in a gene of coenzyme Q10 biosynthesis (COQ2, COQ6, ADCK4, or PDSS2). In these patients the treatment with coenzyme Q10 may be indicated. Also, patients with recessive mutations in PLCE1 may respond fully to the treatment with steroids or cyclosporine A. The patients with CUBN may benefit the treatment with vitamin B12. The detection of causative mutations may also be very important for familial genetic counseling and for prenatal diagnosis.

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“…4 Outside the cell, RNLS acts as a potent pro-survival signal when it binds to its cell membrane receptor, the plasma membrane calcium adenosine triphosphatase isoform PMCA4, and activates a variety of intracellular signaling pathways including the protein kinase B (AKT), extracellularsignal-regulated kinase (ERK), and signal transducer and activator of transcription 3 (STAT3) pathways. [5][6][7] Administration of RNLS minimizes injury in in vivo models of myocardial infarction, 8 ischemic tubular necrosis, 9 and acute pancreatitis. S1 Conversely, RNLS deficiency in RNLS knockout mice exacerbates cisplatin-mediated acute and chronic renal injury, which is reversed by administration of RNLS.…”

Section: Supplementary Materialsmentioning

confidence: 99%