title: Molecular analysis of the CLCN5 gene in Dent's disease: first mutation identified in a patient from South America.
abstract: BACKGROUND
  Dent's disease is a rare renal tubular disorder characterized by low-molecular weight proteinuria, hypercalciuria, nephrocalcinosis, nephrolithiasis, rickets and eventual renal failure. The selective loss of low-molecular weight proteins points to a defect of the proximal tubule, where filtered proteins are normally reabsorbed by endocytosis. The disease tends to present in childhood or early adult life, and males are more severely affected than females. The disease is caused by mutations in CLCN5 or OCRL1, both on the X chromosome, which code for the chloride/proton exchange transporter ClC-5 and the phosphatidylinositol-4,5-biphosphate-5-phosphatase, respectively.
  
  
  METHODS
  Mutational analysis of CLCN5 gene from 4 unrelated patients diagnosed with Dent's disease and their relatives, 3 from Spain and 1 from Bolivia, was performed by PCR and automatic DNA sequencing.
  
  
  RESULTS
  In the current study, we report the identification of 4 mutations in CLCN5 of 1 family from Bolivia and 3 families from Spain. Two of the mutations are novel and consist of 1 nonsense mutation, Y502X, and 1 missense mutation, L225P, affecting ClC-5alpha-helix F, one of the helices involved in formation of the chloride selectivity filter.
  
  
  CONCLUSIONS
  Our results add to the expanding spectrum of mutations in CLCN5. This is the first report of a CLCN5 mutation in a Dent's disease patient of South American origin.
authors.affiliation: Unidad de Investigación, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Ramos-Trujillo
authors.forename: V
authors.initials: V
authors.lastname: Garcia-Nieto
authors.forename: H
authors.initials: H
authors.lastname: Gonzalez-Acosta
authors.forename: J
authors.initials: J
authors.lastname: Vara
authors.forename: V
authors.initials: V
authors.lastname: Pérez-Diaz
authors.forename: I
authors.initials: I
authors.lastname: Nadal
authors.forename: R
authors.initials: R
authors.lastname: Oliveros
authors.forename: F
authors.initials: F
authors.lastname: Claverie-Martin
mesh_terms: D001838:Bolivia; D018118:Chloride Channels / Q000235:genetics*; D004252:DNA Mutational Analysis; D006801:Humans; D053565:Hypercalciuria / Q000150:complications / Q000235:genetics*; D008297:Male; D009154:Mutation; D009397:Nephrocalcinosis / Q000150:complications / Q000235:genetics*; D053040:Nephrolithiasis / Q000150:complications / Q000235:genetics*; D010375:Pedigree; D011507:Proteinuria / Q000150:complications / Q000235:genetics*; D051437:Renal Insufficiency / Q000150:complications / Q000235:genetics*; D012279:Rickets / Q000150:complications / Q000235:genetics*; D013030:Spain
chemical_list: C097503:CLC-5 chloride channel; D018118:Chloride Channels