Mutation analysis of NPHS1 in a worldwide cohort of congenital nephrotic syndrome patients

Nephron Clin Pract. 2012;120(3):c139-46. doi: 10.1159/000337379. Epub 2012 May 11.

Abstract

Background: Congenital nephrotic syndrome (CNS) is defined as nephrotic syndrome that manifests within the first 3 months of life. Mutations in the NPHS1 gene encoding nephrin, are a major cause for CNS. Currently, more than 173 different mutations of NPHS1 have been published as causing CNS, affecting most exons.

Methods: We performed mutation analysis of NPHS1 in a worldwide cohort of 20 families (23 children) with CNS. All 29 exons of the NPHS1 gene were examined using direct sequencing. New mutations were confirmed by demonstrating their absence in 96 healthy control individuals.

Results: We detected disease-causing mutations in 9 of 20 families (45%). Seven of the families showed a homozygous mutation, while two were compound heterozygous. In another 2 families, single heterozygous NPHS1 mutations were detected. Out of 10 different mutations discovered, 3 were novel, consisting of 1 splice site mutation and 2 missense mutations.

Conclusion: Our data demonstrate that the spectrum of NPHS1 mutations is still expanding, involving new exons, in patients from a diverse ethnic background.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Asian People / genetics
  • Case-Control Studies
  • Cohort Studies
  • DNA Mutational Analysis
  • Exons / genetics
  • Female
  • Heterozygote
  • Homozygote
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Membrane Proteins / genetics*
  • Nephrotic Syndrome / congenital*
  • Nephrotic Syndrome / genetics*
  • White People / genetics

Substances

  • Membrane Proteins
  • nephrin