Thirteen novel NPHS1 mutations in a large cohort of children with congenital nephrotic syndrome.

Journal Article (Journal Article)

BACKGROUND: Congenital nephrotic syndrome (CNS) is de- fined as nephrotic syndrome that manifests at birth or within the first 3 months of life. Most patients develop end-stage renal disease (ESRD) within 2 to 3 years of life. CNS of the Finnish-type (CNF) features a rather specific renal histology and is caused by recessive mutations in the NPHS1 gene encoding nephrin, a major structural protein of the glomerular slit-diaphragm. So far, more than 80 different mutations of NPHS1 causing CNF have been published. METHODS: Here, we performed mutation analysis of NPHS1 by exon sequencing in a worldwide cohort of 32 children with CNS from 29 different families. RESULTS: Sixteen of the 29 families (55%) were found to have two disease-causing alleles in NPHS1. Two additional patients had a single heterozygous mutation in NPHS1. Thirteen of a total of 20 different mutations detected were novel (65%). These were five missense mutations, one nonsense mutation, three deletions, one insertion and three splice-site mutations. CONCLUSION: Our data expand the spectrum of known NPHS1 mutations by >15% in a worldwide cohort. Surprisingly, two patients with disease-causing mutations showed a relatively mild phenotype, as one patient had a partial remission with steroid treatment and one patient had normal renal function 1 year after the onset of disease. The increased number of known mutations will facilitate future studies into genotype/phenotype correlations.

Full Text

Duke Authors

Cited Authors

  • Heeringa, SF; Vlangos, CN; Chernin, G; Hinkes, B; Gbadegesin, R; Liu, J; Hoskins, BE; Ozaltin, F; Hildebrandt, F; Members of the APN Study Group,

Published Date

  • November 2008

Published In

Volume / Issue

  • 23 / 11

Start / End Page

  • 3527 - 3533

PubMed ID

  • 18503012

Pubmed Central ID

  • PMC2720813

Electronic International Standard Serial Number (EISSN)

  • 1460-2385

Digital Object Identifier (DOI)

  • 10.1093/ndt/gfn271


  • eng

Conference Location

  • England