Variability in phenotype induced by the podocin variant R229Q plus a single pathogenic mutation.

Journal Article (Journal Article)

BACKGROUND: Mutations in podocin (NPHS2) are the most common cause of childhood onset autosomal recessive steroid-resistant nephrotic syndrome (SRNS). The disease is characterized by early-onset proteinuria, resistance to immunosuppressive therapy and rapid progression to end-stage renal disease. Compound heterozygous changes involving the podocin variant R229Q combined with another pathogenic mutation have been associated with a mild phenotype with disease onset often in adulthood. METHODS: We screened 19 families with early-onset SRNS for mutations in NPHS2 and WT1 and identified four disease-causing mutations (three in NPHS2 and one in WT1) prior to planned whole-exome sequencing. RESULTS: We describe two families with three individuals presenting in childhood who are compound heterozygous for R229Q and one other pathogenic NPHS2 mutation, either L327F or A297V. One child presented at age 4 years (A297V plus R229Q) and the other two at age 13 (L327F plus R229Q), one with steadily deteriorating renal function. CONCLUSIONS: These cases highlight the phenotypic variability associated with the NPHS2 R229Q variant plus pathogenic mutation. Individuals may present with early aggressive disease.

Full Text

Duke Authors

Cited Authors

  • Phelan, PJ; Hall, G; Wigfall, D; Foreman, J; Nagaraj, S; Malone, AF; Winn, MP; Howell, DN; Gbadegesin, R

Published Date

  • October 2015

Published In

Volume / Issue

  • 8 / 5

Start / End Page

  • 538 - 542

PubMed ID

  • 26413278

Pubmed Central ID

  • PMC4581382

International Standard Serial Number (ISSN)

  • 2048-8505

Digital Object Identifier (DOI)

  • 10.1093/ckj/sfv063


  • eng

Conference Location

  • England