title: Phenotypic variability of Dent disease in a large New Zealand kindred.
abstract: Dent disease 1 is a rare cause of chronic kidney disease (CKD) in childhood secondary to mutations in the gene encoding the chloride-proton exchanger, CLC-5, which is found mainly in the proximal tubule. Clinical manifestations are variable and there are no known genotype-phenotype correlations.
  
  
  
  The proband was identified as having a mutation in CLCN5. The extended family of the proband was invited to participate in a study of Dent disease after several males were noted to have a history of CKD. Urine retinol binding protein, urine calcium, serum creatinine, and DNA samples were collected for analysis. Ten hemizygous males and 6 heterozygous females were identified. Advanced CKD was detected in 3 males (1 child). Renal biopsies in 4 children showed both glomerular and tubulo-interstitial changes. There was no correlation between age and disease severity.
  
  
  
  This is the first reported family from the southern hemisphere with this condition. A novel CLCN5 mutation is described, c.1618G>C (p.Ala540Pro). The severity of renal disease varies greatly among individuals.
authors.affiliation: Department of Paediatric Nephrology, Starship Children's Hospital, Private Bag 92024, Park Road, Auckland, New Zealand. wwong@adhb.govt.nz.
authors.forename: William
authors.identifier: 0000-0002-8031-7408
authors.initials: W
authors.lastname: Wong
authors.affiliation: Genetic Health Service New Zealand Central Hub, Wellington, New Zealand.
authors.forename: Gemma
authors.initials: G
authors.lastname: Poke
authors.affiliation: Department of Paediatric Nephrology, Starship Children's Hospital, Private Bag 92024, Park Road, Auckland, New Zealand.
authors.forename: Maria
authors.initials: M
authors.lastname: Stack
authors.affiliation: Department of Paediatric Nephrology, Starship Children's Hospital, Private Bag 92024, Park Road, Auckland, New Zealand.
authors.forename: Tonya
authors.initials: T
authors.lastname: Kara
authors.affiliation: Department of Paediatric Nephrology, Starship Children's Hospital, Private Bag 92024, Park Road, Auckland, New Zealand.
authors.forename: Chanel
authors.initials: C
authors.lastname: Prestidge
authors.affiliation: Wellington Regional Genetics Laboratory, Wellington, New Zealand.
authors.forename: Kim
authors.initials: K
authors.lastname: Flintoff
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D018118:Chloride Channels / Q000235:genetics*; D005260:Female; D040181:Genetic Diseases, X-Linked / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D053565:Hypercalciuria / Q000652:urine; D007669:Kidney Calculi / Q000000981:diagnostic imaging / Q000209:etiology; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D053040:Nephrolithiasis / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D009520:New Zealand; D010641:Phenotype; D011507:Proteinuria / Q000652:urine; D051436:Renal Insufficiency, Chronic / Q000209:etiology; D014463:Ultrasonography
chemical_list: C097503:CLC-5 chloride channel; D018118:Chloride Channels
keywords: CLCN5; Correlation; Dent disease; Phenotype genotype