title: Thirteen novel NPHS1 mutations in a large cohort of children with congenital nephrotic syndrome.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pediatrics, University of Michigan, Ann Arbor, MI 48109-5646, USA.
authors.forename: Saskia F
authors.initials: SF
authors.lastname: Heeringa
authors.forename: Christopher N
authors.initials: CN
authors.lastname: Vlangos
authors.forename: Gil
authors.initials: G
authors.lastname: Chernin
authors.forename: Bernward
authors.initials: B
authors.lastname: Hinkes
authors.forename: Rasheed
authors.initials: R
authors.lastname: Gbadegesin
authors.forename: Jinhong
authors.initials: J
authors.lastname: Liu
authors.forename: Bethan E
authors.initials: BE
authors.lastname: Hoskins
authors.forename: Fatih
authors.initials: F
authors.lastname: Ozaltin
authors.forename: Friedhelm
authors.initials: F
authors.lastname: Hildebrandt
mesh_terms: D018389:Codon, Nonsense / Q000235:genetics; D015331:Cohort Studies; D005260:Female; D017353:Gene Deletion; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D016254:Mutagenesis, Insertional / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D020125:Mutation, Missense / Q000235:genetics; D009404:Nephrotic Syndrome / Q000151:congenital* / Q000235:genetics*; D010641:Phenotype
chemical_list: D018389:Codon, Nonsense; D008565:Membrane Proteins; C113267:nephrin