title: Analysis of NPHS1, NPHS2, ACTN4, and WT1 in Japanese patients with congenital nephrotic syndrome.
abstract: BACKGROUND
  Congenital nephrotic syndrome (CNS) causes significant renal failure, and is classified into two types: (1) Finnish type; and (2) other, including diffuse mesangial sclerosis. Mutations of NPHS1 and NPHS2, which encode the slit diaphragm components nephrin and podocin, cause CNS and autosomal-recessive familial steroid-resistant nephrotic syndrome, respectively. Most patients with Finnish-type CNS in Europe and the United States have NPHS1 mutations. However, NPHS2 mutations have been detected in some cases. Mutations in ACTN4, encoding alpha-actinin-4, cause an autosomal-dominant focal segmental glomerulosclerosis. alpha-actinin-4 stabilizes the podocyte cytoskeleton structure, connecting with actin filaments. WT1 mutations, causing Wilm's tumor, have been demonstrated in some CNS patients with diffuse mesangial sclerosis. Systematic investigation of genes for CNS in Japan has never been performed.
  
  
  METHODS
  To clarify the role of mutations in these four genes, we used polymerase chain reaction (PCR) and direct sequencing to investigate all exons and exon-intron boundaries for these genes in 13 unrelated CNS patients from regional pediatric kidney disease centers in Japan.
  
  
  RESULTS
  A novel homozygous nonsense mutation of NPHS1, E246X in exon 7, and a novel homozygous deletion mutation of NPHS1, 2156_2163del in exon 16 were detected in one patient each. A novel homozygous nonsense mutation of NPHS2, R196X in exon 5, was found in one patient, and the same heterozygous nonsense mutation was detected in another. No ACTN4 or WT1 mutations were detected.
  
  
  CONCLUSIONS
  These studies demonstrate that mutation of NPHS1 is not a major cause of CNS in Japanese patients, and that mutation of NPHS2 can be responsible for CNS in this population.
authors.affiliation: Department of Pediatrics, Wakayama Medical University, Wakayama City, Wakayma, Japan.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Sako
authors.forename: Koichi
authors.initials: K
authors.lastname: Nakanishi
authors.forename: Mina
authors.initials: M
authors.lastname: Obana
authors.forename: Nahoko
authors.initials: N
authors.lastname: Yata
authors.forename: Sakurako
authors.initials: S
authors.lastname: Hoshii
authors.forename: Shori
authors.initials: S
authors.lastname: Takahashi
authors.forename: Naohiro
authors.initials: N
authors.lastname: Wada
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Yoshitsugu
authors.initials: Y
authors.lastname: Kaku
authors.forename: Kenichi
authors.initials: K
authors.lastname: Satomura
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ikeda
authors.forename: Masataka
authors.initials: M
authors.lastname: Honda
authors.forename: Kazumoto
authors.initials: K
authors.lastname: Iijima
authors.forename: Norishige
authors.initials: N
authors.lastname: Yoshikawa
mesh_terms: D000185:Actinin / Q000235:genetics*; D001483:Base Sequence; D018389:Codon, Nonsense; D017931:DNA Primers; D005387:Finland; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007564:Japan; D008565:Membrane Proteins / Q000235:genetics*; D008840:Microfilament Proteins / Q000235:genetics*; D009404:Nephrotic Syndrome / Q000151:congenital* / Q000235:genetics*; D044469:Racial Groups / Q000235:genetics; D014481:United States; D025721:WT1 Proteins / Q000235:genetics*
chemical_list: C111453:ACTN4 protein, human; D018389:Codon, Nonsense; D017931:DNA Primers; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D008840:Microfilament Proteins; C407223:NPHS2 protein; D025721:WT1 Proteins; C113267:nephrin; D000185:Actinin