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Nephrol Dial Transplant. 2008 Nov;23(11):3527-33. doi: 10.1093/ndt/gfn271. Epub 2008 May 23.

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

Author information

1
Department of Pediatrics, University of Michigan, Ann Arbor, MI 48109-5646, USA.

Abstract

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.

PMID:
18503012
PMCID:
PMC2720813
DOI:
10.1093/ndt/gfn271
[Indexed for MEDLINE]
Free PMC Article

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