Clinical utility of genetic testing in children and adults with steroid-resistant nephrotic syndrome

Clin J Am Soc Nephrol. 2011 May;6(5):1139-48. doi: 10.2215/CJN.05260610. Epub 2011 Mar 17.


Background and objectives: The increasing number of podocyte-expressed genes implicated in steroid-resistant nephrotic syndrome (SRNS), the phenotypic variability, and the uncharacterized relative frequency of mutations in these genes in pediatric and adult patients with SRNS complicate their routine genetic analysis. Our aim was to compile the clinical and genetic data of eight podocyte genes analyzed in 110 cases (125 patients) with SRNS (ranging from congenital to adult onset) to provide a genetic testing approach.

Design, setting, participants, & measurements: Mutation analysis was performed by sequencing the NPHS1, NPHS2, TRPC6, CD2AP, PLCE1, INF2, WT1 (exons 8 and 9), and ACTN4 (exons 1 to 10) genes.

Results: We identified causing mutations in 34% (37/110) of SRNS patients, representing 67% (16/24) familial and 25% (21/86) sporadic cases. Mutations were detected in 100% of congenital-onset, 57% of infantile-onset, 24 and 36% of early and late childhood-onset, 25% of adolescent-onset, and 14% of adult-onset patients. The most frequently mutated gene was NPHS1 in congenital onset and NPHS2 in the other groups. A partial remission was observed in 7 of 26 mutation carriers treated with immunosuppressive agents and/or angiotensin-converting enzyme inhibitors. Patients with NPHS1 mutations showed a faster progression to ESRD than patients with NPHS2 mutations. None of these mutation carriers relapsed after kidney transplantation.

Conclusions: We propose a genetic testing algorithm for SRNS based on the age at onset and the familial/sporadic status. Mutation analysis of specific podocyte-genes has a clinical value in all age groups, especially in children.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adolescent
  • Adult
  • Algorithms
  • Child
  • Child, Preschool
  • Cytoskeletal Proteins / genetics
  • Drug Resistance / genetics*
  • Formins
  • Genetic Testing / methods*
  • Genotype
  • Humans
  • Infant
  • Infant, Newborn
  • Intracellular Signaling Peptides and Proteins / genetics
  • Membrane Proteins / genetics
  • Microfilament Proteins / genetics
  • Nephrotic Syndrome / drug therapy*
  • Nephrotic Syndrome / genetics*
  • Phenotype
  • Phosphoinositide Phospholipase C / genetics
  • Steroids / therapeutic use*
  • TRPC Cation Channels / genetics
  • TRPC6 Cation Channel
  • WT1 Proteins / genetics
  • Young Adult


  • Adaptor Proteins, Signal Transducing
  • CD2-associated protein
  • Cytoskeletal Proteins
  • Formins
  • INF2 protein, human
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Microfilament Proteins
  • NPHS2 protein
  • Steroids
  • TRPC Cation Channels
  • TRPC6 Cation Channel
  • TRPC6 protein, human
  • WT1 Proteins
  • nephrin
  • Phosphoinositide Phospholipase C
  • phospholipase C epsilon