RT Journal Article
SR Electronic
T1 Molecular genetic analysis of Steroid Resistant Nephrotic Syndrome: Detection of a novel mutation
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 305987
DO 10.1101/305987
A1 Niloofar Serajpour
A1 Behnaz Karimi
A1 Nakisa Hooman
A1 Rozita Hosseini
A1 Pedram Khosravi
A1 Hila Milo Rasouly
A1 Azadeh Shojaei
YR 2018
UL http://biorxiv.org/content/early/2018/04/22/305987.abstract
AB 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.Detection of a novel mutation in SRNS