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

Nephrol Dial Transplant 2008 Nov 23;23(11):3527-33. Epub 2008 May 23.

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

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.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2720813PMC
November 2008
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References

(Supplied by CrossRef)

Huttunen et al.
Archives of Disease in Childhood 1976

Joppich et al.
Annales paediatriae Fenniae 1966

1999

Kuusniemi et al.
Kidney international 2006

Ruotsalainen et al.
PNAS 1999

Khoshnoodi et al.
American Journal Of Pathology 2003

Patari-Sampo et al.
Annals of medicine 2006

Kestil   et al.
Molecular cell 1998

Beltcheva et al.
Human mutation 2001

Pediatrics 2007

MUCHA et al.
Pediatric Research 2006

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