title: Chloride channel CLCN5 mutations in Japanese children with familial idiopathic low molecular weight proteinuria.
abstract: BACKGROUND
  Familial idiopathic low molecular weight proteinuria (FILMWP) is a renal proximal tubulopathy characterized by mild proteinuria consisting of low molecular weight proteinuria and relatively conserved renal function in young patients, but without rickets. Mutations in the renal chloride channel CLCN5 gene have been reported in three disorders of hypercalciuric nephrolithiasis and in FILMWP.
  
  
  METHODS
  To assess the relationship between molecular defects and phenotypic variations, we analyzed the CLCN5 gene from three additional Japanese families with FILMWP using single-strand conformation polymorphism and sequencing.
  
  
  RESULTS
  We identified three mutations: a single base insertion at codon 514; a single base deletion at codon 116; and a nonsense mutation, R704X. The R704X mutation is identical to that found in X-linked recessive nephrolithiasis, but there was no renal failure in our patient. The first two mutations caused a shift in the reading frame, and all introduced a premature stop codon, resulting in synthesis of truncated CLC-5 proteins that lacked 220 (29%), 610 (82%), and 43 (6%) amino acids, respectively. These mutations were demonstrated to cosegregate with the disease in each of the three families.
  
  
  CONCLUSIONS
  We conclude that the CLCN5 gene is responsible for the renal proximal tubulopathy in many Japanese families and suggest that molecular defects, environmental factors, or other modifying genes may account for the different phenotypes.
authors.affiliation: Department of Pediatrics, Kumamoto University School of Medicine, Kumamoto, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Nakazato
authors.forename: J
authors.initials: J
authors.lastname: Yoshimuta
authors.forename: S
authors.initials: S
authors.lastname: Karashima
authors.forename: S
authors.initials: S
authors.lastname: Matsumoto
authors.forename: F
authors.initials: F
authors.lastname: Endo
authors.forename: I
authors.initials: I
authors.lastname: Matsuda
authors.forename: S
authors.initials: S
authors.lastname: Hattori
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D018118:Chloride Channels / Q000737:chemistry / Q000235:genetics*; D018389:Codon, Nonsense / Q000235:genetics; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D017931:DNA Primers / Q000235:genetics; D005260:Female; D006801:Humans; D007564:Japan; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D018807:Polymorphism, Single-Stranded Conformational; D011507:Proteinuria / Q000235:genetics* / Q000378:metabolism; D017384:Sequence Deletion
chemical_list: C097503:CLC-5 chloride channel; D018118:Chloride Channels; D018389:Codon, Nonsense; D017931:DNA Primers; D004247:DNA