title: NUP107 mutations in children with steroid-resistant nephrotic syndrome.
abstract: BACKGROUND
  NUP107 is a novel gene associated with autosomal recessive steroid-resistant nephrotic syndrome (SRNS) with focal segmental glomerulosclerosis (FSGS) in children. The frequency of NUP107 mutations in children with SR-FSGS remains unknown.
  
  
  METHODS
  Nine families with two siblings affected by childhood-onset SRNS or proteinuria were recruited. FSGS was confirmed by a kidney biopsy in at least one affected sibling in all families. Additionally, 69 sporadic pediatric cases with biopsy-proven SR-FSGS who had not responded to any treatment were included. All coding exons with flanking introns of the NUP107 gene were amplified using polymerase chain reaction and directly sequenced.
  
  
  RESULTS
  Biallelic NUP107 mutations were detected in four pairs (44.4%) of siblings from the familial cases and three (4.3%) sporadic cases. All affected patients harbored the p.Asp831Ala mutation in one allele and a truncating or abnormal splicing mutation in the other allele. NUP107 mutation-positive patients showed an earlier onset age (39.4 ± 13.1 versus 76.8 ± 50.0 months, P= 0.027) and more rapid progression to end-stage renal disease (at the ages of 58.9 ± 23.4 versus 123.1 ± 62.7 months, P < 0.001) compared with mutation-negative patients. None of the eight mutation-positive cases, who underwent kidney transplantation, showed recurrence of FSGS in the graft kidney, while 35.3% of mutation-negative cases showed recurrence of FSGS.
  
  
  CONCLUSIONS
  An unexpectedly high incidence of NUP107 mutations was observed in Korean children with SR-FSGS. Initial genetic screening of children with SR-FSGS should include the NUP107 gene, at least in Korea. Further studies are necessary to determine the incidences of NUP107 mutations in other countries.
authors.affiliation: Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Korea.
authors.forename: Eujin
authors.initials: E
authors.lastname: Park
authors.affiliation: Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Korea.
authors.forename: Yo Han
authors.initials: YH
authors.lastname: Ahn
authors.affiliation: Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Korea.|Research Coordination Center for Rare Diseases, Seoul National University Hospital, Seoul, Korea.
authors.forename: Hee Gyung
authors.initials: HG
authors.lastname: Kang
authors.affiliation: Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Miyake
authors.affiliation: Second Department of Internal Medicine, Kansai Medical University, Osaka, Japan.
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Tsukaguchi
authors.affiliation: Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Korea.|Research Coordination Center for Rare Diseases, Seoul National University Hospital, Seoul, Korea.|Kidney Research Institute, Medical Research Center, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Hae Il
authors.initials: HI
authors.lastname: Cheong
mesh_terms: D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D007223:Infant; D007668:Kidney / Q000473:pathology; D016030:Kidney Transplantation; D008297:Male; D009154:Mutation; D009404:Nephrotic Syndrome / Q000151:congenital* / Q000235:genetics / Q000601:surgery; D028861:Nuclear Pore Complex Proteins / Q000235:genetics*; D010375:Pedigree
chemical_list: C512772:NUP107 protein, human; D028861:Nuclear Pore Complex Proteins
keywords: NUP107; end-stage renal disease; focal segmental glomerulosclerosis; mutation; steroid-resistant nephrotic syndrome