title: Nineteen novel NPHS1 mutations in a worldwide cohort of patients with congenital nephrotic syndrome (CNS).
abstract: BACKGROUND
  Recessive mutations in the NPHS1 gene encoding nephrin account for approximately 40% of infants with congenital nephrotic syndrome (CNS). CNS is defined as steroid-resistant nephrotic syndrome (SRNS) within the first 90 days of life. Currently, more than 119 different mutations of NPHS1 have been published affecting most exons.
  
  
  METHODS
  We here performed mutational analysis of NPHS1 in a worldwide cohort of 67 children from 62 different families with CNS.
  
  
  RESULTS
  We found bi-allelic mutations in 36 of the 62 families (58%) confirming in a worldwide cohort that about one-half of CNS is caused by NPHS1 mutations. In 26 families, mutations were homozygous, and in 10, they were compound heterozygous. In an additional nine patients from eight families, only one heterozygous mutation was detected. We detected 37 different mutations. Nineteen of the 37 were novel mutations (approximately 51.4%), including 11 missense mutations, 4 splice-site mutations, 3 nonsense mutations and 1 small deletion. In an additional patient with later manifestation, we discovered two further novel mutations, including the first one affecting a glycosylation site of nephrin.
  
  
  CONCLUSIONS
  Our data hereby expand the spectrum of known mutations by 17.6%. Surprisingly, out of the two siblings with the homozygous novel mutation L587R in NPHS1, only one developed nephrotic syndrome before the age of 90 days, while the other one did not manifest until the age of 2 years. Both siblings also unexpectedly experienced an episode of partial remission upon steroid treatment.
authors.affiliation: Department of Pediatrics, University of Michigan, 1150 W. Medical Center Drive Drive, Ann Arbor, MI, USA.
authors.forename: Dominik S
authors.initials: DS
authors.lastname: Schoeb
authors.forename: Gil
authors.initials: G
authors.lastname: Chernin
authors.forename: Saskia F
authors.initials: SF
authors.lastname: Heeringa
authors.forename: Verena
authors.initials: V
authors.lastname: Matejas
authors.forename: Susanne
authors.initials: S
authors.lastname: Held
authors.forename: Virginia
authors.initials: V
authors.lastname: Vega-Warner
authors.forename: Detlef
authors.initials: D
authors.lastname: Bockenhauer
authors.forename: Christopher N
authors.initials: CN
authors.lastname: Vlangos
authors.forename: Khemchand N
authors.initials: KN
authors.lastname: Moorani
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Neuhaus
authors.forename: Jameela A
authors.initials: JA
authors.lastname: Kari
authors.forename: James
authors.initials: J
authors.lastname: MacDonald
authors.forename: Pawaree
authors.initials: P
authors.lastname: Saisawat
authors.forename: Shazia
authors.initials: S
authors.lastname: Ashraf
authors.forename: Bugsu
authors.initials: B
authors.lastname: Ovunc
authors.forename: Martin
authors.initials: M
authors.lastname: Zenker
authors.forename: Friedhelm
authors.initials: F
authors.lastname: Hildebrandt
mesh_terms: D015331:Cohort Studies; D005091:Exons / Q000235:genetics; D005190:Family; D005260:Female; D005838:Genotype; D014943:Global Health; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D009404:Nephrotic Syndrome / Q000151:congenital* / Q000235:genetics* / Q000473:pathology; D010641:Phenotype; D011379:Prognosis
chemical_list: D008565:Membrane Proteins; C113267:nephrin