title: Mutations of CLCN5 in Japanese children with idiopathic low molecular weight proteinuria, hypercalciuria and nephrocalcinosis.
abstract: The annual urinary screening of Japanese children above three years of age has identified a progressive renal tubular disorder characterized by low molecular weight proteinuria, hypercalciuria and nephrocalcinosis. The disorder has been observed in over 60 patients and has a familial predisposition. Mutations of a renal chloride channel gene, CLCN5, have been reported in four such families, and we have undertaken studies in additional patients from 10 unrelated, non-consanguineous Japanese families to further characterize such CLCN5 mutations and to ascertain their prevalence. CLCN5 abnormalities we identified in 7 of the 10 unrelated patients and consisted of 5 mutations (2 nonsense, 1 frameshift and 2 missense), 1 deletion and 1 silent polymorphism. A clustering of these mutations in CLCN5 exons 8 and 10 was observed. Over 80% of the CLCN5 mutations could be readily detected by single stranded conformational polymorphism (SSCP) analysis, thereby providing a useful mutation screening method. Our results, which indicate that over 70% of Japanese patients with this renal tubulopathy have CLCN5 mutations, will help in the genetic and clinical evaluation of children at risk from this disorder.
authors.affiliation: MRC Clinical Sciences Centre, Royal Postgraduate Medical School, Hammersmith Hospital, London, England.
authors.forename: N
authors.initials: N
authors.lastname: Akuta
authors.forename: S E
authors.initials: SE
authors.lastname: Lloyd
authors.forename: T
authors.initials: T
authors.lastname: Igarashi
authors.forename: H
authors.initials: H
authors.lastname: Shiraga
authors.forename: T
authors.initials: T
authors.lastname: Matsuyama
authors.forename: S
authors.initials: S
authors.lastname: Yokoro
authors.forename: J P
authors.initials: JP
authors.lastname: Cox
authors.forename: R V
authors.initials: RV
authors.lastname: Thakker
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D002118:Calcium / Q000652:urine*; D002648:Child; D002675:Child, Preschool; D018118:Chloride Channels / Q000235:genetics*; D004247:DNA / Q000235:genetics; D005260:Female; D006801:Humans; D007564:Japan / Q000208:ethnology; D008297:Male; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009154:Mutation; D009397:Nephrocalcinosis / Q000150:complications*; D018807:Polymorphism, Single-Stranded Conformational; D015995:Prevalence; D011506:Proteins / Q000737:chemistry; D011507:Proteinuria / Q000150:complications / Q000235:genetics* / Q000652:urine*
chemical_list: C097503:CLC-5 chloride channel; D018118:Chloride Channels; D011506:Proteins; D004247:DNA; D002118:Calcium