title: WT1 and NPHS2 gene mutation analysis and clinical management of steroid-resistant nephrotic syndrome.
abstract: Nephrotic syndrome (NS) is a kidney disease predominantly present in children with idiopathic condition; final stage of the disease progresses into end-stage renal disease. Generally, NS is treated using standard steroid therapy, however; most of the children are steroid sensitive and about 15-20% are non-responders (SRNS). Non-responsiveness of these children would be a risk with the possibility of mutational changes in podocyte genes (NPHS1, NPHS2, WT1, PLCE1). The mutation in podocyte genes is associated with SRNS. NPHS1, NPHS2, and WT1 genes are identified/directly linked to SRNS. The present study is a surveillance on the mutation analysis of WT1 (exons 8 and 9) and NPHS2 (exons 1-8) gene in SRNS followed by clinical management. In the present study, we analyzed these two genes in a total of 117 SRNS (73 boys and 44 girls) children. A total of five mutations were detected in six children. First, WT1 mutation was detected at 9th intron-IVS 9 + 4C > T position in one SRNS female patient. This WT1 mutation was identified in a girl having Frasier Syndrome (FS) with focal segmental glomerulosclerosis and a complete sex reversal found through molecular and karyological screening. In NPHS2, missense mutations of P20L (in two children), P316S, and p.R229Q, and a frame shift mutation of 42delG were detected. Thus, applying molecular investigation helped us to decide on treatment plan of SRNS patients, mainly to avoid unnecessary immunosuppressive treatment.
authors.affiliation: Department of Pediatric Nephrology, Institute of Child Health and Hospital for Children, Madras Medical College, Halls Road, Egmore, Chennai, Tamil Nadu, 600 008, India.|Department of Medical Genetics, The Tamil Nadu Dr. M.G.R. Medical University, Anna Salai, Guindy, Chennai, Tamil Nadu, 600 032, India.
authors.forename: Aravind Selvin Kumar
authors.initials: AS
authors.lastname: Ramanathan
authors.affiliation: Department of Biotechnology & Genetic Engineering, School of Biotechnology, Bharathidasan University, Tiruchirappalli, Tamil Nadu, 620 024, India.
authors.forename: Murali
authors.initials: M
authors.lastname: Vijayan
authors.affiliation: Department of Medical Genetics, The Tamil Nadu Dr. M.G.R. Medical University, Anna Salai, Guindy, Chennai, Tamil Nadu, 600 032, India.
authors.forename: Srilakshmi
authors.initials: S
authors.lastname: Rajagopal
authors.affiliation: Department of Pediatric Nephrology, Institute of Child Health and Hospital for Children, Madras Medical College, Halls Road, Egmore, Chennai, Tamil Nadu, 600 008, India.
authors.forename: Padmaraj
authors.initials: P
authors.lastname: Rajendiran
authors.affiliation: Department of Pediatric Nephrology, Institute of Child Health and Hospital for Children, Madras Medical College, Halls Road, Egmore, Chennai, Tamil Nadu, 600 008, India. prabha.sengu@gmail.com.|Department of Pediatric Nephrology, Dr. Mehta's Children's Hospital, McNichols Rd, 3rd Lane, Chetpet, Chennai, Tamil Nadu, 600 031, India. prabha.sengu@gmail.com.
authors.forename: Prabha
authors.initials: P
authors.lastname: Senguttuvan
mesh_terms: D002648:Child; D002675:Child, Preschool; D004351:Drug Resistance / Q000235:genetics*; D005260:Female; D016368:Frameshift Mutation; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D020125:Mutation, Missense; D009404:Nephrotic Syndrome / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D050199:Podocytes / Q000378:metabolism / Q000473:pathology; D013256:Steroids / Q000627:therapeutic use; D025721:WT1 Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C407223:NPHS2 protein; D013256:Steroids; D025721:WT1 Proteins; C583751:WT1 protein, human
keywords: FSGS; Indian children; NPHS2; NS; SRNS; Wilms’ tumor