Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 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

Saskia F Heeringa  1 , Christopher N Vlangos, Gil Chernin, Bernward Hinkes, Rasheed Gbadegesin, Jinhong Liu, Bethan E Hoskins, Fatih Ozaltin, Friedhelm Hildebrandt; Members of the APN Study Group
Collaborators, Affiliations

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

Saskia F Heeringa et al. Nephrol Dial Transplant. 2008 Nov.

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.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
Nephrin protein domain structure relative to NPHS1 mutations. Domains consist of 8 extra-cellular Ig-like domains (numbered 1-8), a Fibronectin type III like module (Fn), a transmembrane domain and an intracellular domain. All amino acid changes found in this study are shown. Novel mutations are in bold. Mutations are spread throughout the protein with predominance of Ig-like domain 5. No mutations were found in Ig-like domains 3 and 7. The positions of three free cysteine residues are indicated by closed dots. (Kestilä, 1998)
See this image and copyright information in PMC

References

    1. Huttunen NP. Congenital nephrotic syndrome of Finnish type. Study of 75 patients. Arch Dis Child. 1976;51(Suppl 5):344–348. - PMC - PubMed
    1. Norio R. Heredity in the congenital nephrotic syndrome. A genetic study of 57 Finnish families with a review of reported cases. Ann Paediatr Fenn. 1966;12(Suppl 27):1–94. - PubMed
    1. Holmberg C, Trygvasson K, Kestilaa MK, et al. Pediatric Nephrology. 5th edn. Baltimore, MD: Lippincott Williams & Wilkins; 2004. Congenital nephrotic syndrome; pp. 503–516.
    1. Qvist E, Laine J, Ronnholm K, et al. Graft function 5–7 years after renal transplantation in early childhood. Transplantation. 1999;67:1043. - PubMed
    1. Kuusniemi A-M, Merenmies J, Lahdenkari A-T, et al. Glomerular sclerosis in kidneys with congenital nephrotic syndrome (NPHS1) Kidney Int. 2006;70:1423–1431. - PubMed

Publication types

LinkOut - more resources