Phenotypic variability of Dent disease in a large New Zealand kindred

Pediatr Nephrol. 2017 Feb;32(2):365-369. doi: 10.1007/s00467-016-3472-8. Epub 2016 Oct 3.

Abstract

Background: 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.

Case diagnosis/treatment: 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.

Conclusions: 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.

Keywords: CLCN5; Correlation; Dent disease; Phenotype genotype.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Child
  • Child, Preschool
  • Chloride Channels / genetics*
  • Female
  • Genetic Diseases, X-Linked / diagnosis
  • Genetic Diseases, X-Linked / genetics*
  • Genetic Diseases, X-Linked / physiopathology
  • Humans
  • Hypercalciuria / urine
  • Kidney Calculi / diagnostic imaging
  • Kidney Calculi / etiology
  • Male
  • Middle Aged
  • Mutation, Missense
  • Nephrolithiasis / diagnosis
  • Nephrolithiasis / genetics*
  • Nephrolithiasis / physiopathology
  • New Zealand
  • Phenotype*
  • Proteinuria / urine
  • Renal Insufficiency, Chronic / etiology
  • Ultrasonography

Substances

  • CLC-5 chloride channel
  • Chloride Channels

Supplementary concepts

  • Dent disease 1