title: Steroid-resistant nephrotic syndrome: impact of genetic testing.
abstract: OBJECTIVE
  Mutations in several genes are known to cause steroid-resistant nephrotic syndome (SRNS), most commonly in NPHS1, NPHS2, and WT1. Our aims were to determine the frequency of mutations in these genes in children with SRNS, the response of patients with SRNS to various immunosuppressants, and the disease outcome, and to review the predictive value of genetic testing and renal biopsy result.
  
  
  METHODS
  A retrospective review was performed of the medical records for all children with SRNS who were treated and followed-up in the Pediatric Nephrology Unit of King Abdulaziz University Hospital (KAUH), Jeddah, Saudi Arabia from 2002-2012.
  
  
  METHODS
  We retrospectively reviewed the medical records of children above 1 year of age, who presented with SRNS to KAUH, Jeddah, Saudi Arabia, in the 10-year interval from 2002-2012 and for whom the results of genetic testing for NPHS1, NPHS2, and WT1 were available. We compared the clinical phenotype, including response to treatment and renal outcome to genotype data.
  
  
  RESULTS
  We identified 44 children with a clinical diagnosis of SRNS in whom results of genetic testing were available. Presumably disease-causing mutations were detected in 5 children (11.4%) of which 3 (6.8%) had NPHS2 mutation and 2 (4.5%) had NPHS1 mutation. Renal biopsy revealed minimal change disease (MCD) or variants in 17 children, focal segmental glomerulosclerosis (FSGS) in 23 children, membranoproliferative changes (MPGN) in 2 children, and IgA nephropathy in another 2 children. Children with MCD on biopsy were more likely to respond to treatment than those with FSGS. None of those with an identified genetic cause showed any response to treatment.
  
  
  CONCLUSIONS
  The frequency of identified disease-causing mutations in children older than 1 year with SRNS presented to KAUH was 11.4%, and these patients showed no response to treatment. Initial testing for gene mutation in children with SRNS may obviate the need for biopsy, and the use of immunosuppressive treatment in children with disease due to NPHS1 or NPHS2 mutations. Renal biopsy was useful in predicting response in those without genetic mutations.
authors.affiliation: Jameela Abdulaziz Kari, Pediatrics, King Abdulaziz University,, PO Box 13042 Jeddah 21943, Saudi Arabia, T: 966-505-677904, F: 966-22-408-8353, jkari@doctors.org.uk.
authors.forename: Jameela A
authors.initials: JA
authors.lastname: Kari
authors.forename: Sherif M
authors.initials: SM
authors.lastname: El-Desoky
authors.forename: Mamdooh
authors.initials: M
authors.lastname: Gari
authors.forename: Khalid
authors.initials: K
authors.lastname: Malik
authors.forename: Virginia
authors.initials: V
authors.lastname: Vega-Warner
authors.forename: Svjetlana
authors.initials: S
authors.lastname: Lovric
authors.forename: Detlef
authors.initials: D
authors.lastname: Bockenhauer
mesh_terms: D001706:Biopsy; D002675:Child, Preschool; D005500:Follow-Up Studies; D005820:Genetic Testing / Q000379:methods; D005838:Genotype; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007223:Infant; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation; D009404:Nephrotic Syndrome / Q000151:congenital* / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology; D010641:Phenotype; D012189:Retrospective Studies; D012529:Saudi Arabia; D016896:Treatment Outcome; D025721:WT1 Proteins / Q000235:genetics*
chemical_list: D007166:Immunosuppressive Agents; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C407223:NPHS2 protein; D025721:WT1 Proteins; C583751:WT1 protein, human; C113267:nephrin