Two heterozygous mutations of CLDN16 in a Japanese patient with FHHNC

Pediatr Nephrol. 2003 Dec;18(12):1280-2. doi: 10.1007/s00467-003-1304-0. Epub 2003 Oct 30.

Abstract

Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC, MIN 248250) is a rare autosomal recessive tubular disorder that eventually progresses to renal failure. However, the progression to end-stage renal failure can vary from patient to patient. A primary defect is related to impaired tubular resorption of magnesium and calcium in the thick ascending limb of Henle's loop. Recently, paracellin-1 was identified as a renal tight junction protein predominantly expressed in TAL. Mutations of its gene (CLDN16) have been shown to cause FHHNC. We describe a sporadic Japanese case of FHHNC. The male patient showed hematuria, hypercalciuria, and nephrocalcinosis at 5 years of age. Hypomagnesemia was also noticed at this time. As renal function gradually deteriorated, further evaluation was performed at 14 years of age and a diagnosis of FHHNC was made. Despite several medications (magnesium supplementation, citrate, and hydrochlorothiazide), he eventually progressed to renal insufficiency at 19 years of age. Analysis of the CLDN16 gene demonstrated two heterozygous mutations (R149Q and R216C). Mutations of the same amino acids have already been described in FHHNC and thus these mutations might be the cause of the disease in our patient. Hence, we confirm the genetic impairment of the CLDN16 gene in a Japanese patient with FHHNC.

Publication types

  • Case Reports

MeSH terms

  • Calcium / urine*
  • Child, Preschool
  • DNA / genetics
  • Exons / genetics
  • Heterozygote
  • Humans
  • Kidney Failure, Chronic / etiology
  • Magnesium / blood*
  • Male
  • Mutation, Missense / genetics*
  • Nephrocalcinosis / blood
  • Nephrocalcinosis / genetics*
  • Nephrocalcinosis / urine
  • Point Mutation / genetics
  • Renal Dialysis
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • DNA
  • Magnesium
  • Calcium