First report of a novel missense CLDN19 mutations causing familial hypomagnesemia with hypercalciuria and nephrocalcinosis in a Chinese family

Calcif Tissue Int. 2015 Apr;96(4):265-73. doi: 10.1007/s00223-014-9951-7. Epub 2015 Jan 4.

Abstract

Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is an autosomal recessive disorder caused by mutations in the CLDN16 or CLDN19 genes, encoding claudin-16 and claudin-19 in the thick ascending limb of Henle's loop. In patients with claudin-19 mutations, severe ocular involvement (macular coloboma, pigmentary retinitis, nystagmus, or visual loss) has been described. In this report, we presented a 12-year-old girl with rickets, polyuria, and polydipsia. She was the daughter of consanguineous parents, and she had a history of recurred hypocalcemic and hypomagnesemic tetany. On physical examination, bilateral horizontal nystagmus and severe myopia were detected. Laboratory examination revealed hypomagnesemia, hypocalcemia, hypercalciuria, nephrocalcinosis, and renal stone. A clinical diagnosis of FHHNC caused possibly by claudin-19 mutation was decided with the ocular findings. DNA analysis revealed a novel homozygous missense mutation c.241C>T in the CLDN19 gene. In conclusion, in a patient with hypomagnesemia, hypercalciuria, nephrocalcinosis, and ocular findings, a diagnosis of FHHNC caused by claudin-19 mutation should be considered. This is the first study of FHHNC in Chinese population. Our findings of the novel mutation c.241C>T in exon 2 add to the list of more than 16 mutations of CLDN19 gene reported.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Child
  • China
  • Claudins / genetics*
  • Consanguinity
  • DNA Mutational Analysis
  • Exons
  • Female
  • Humans
  • Hypercalciuria / genetics*
  • Hypocalcemia / genetics*
  • Magnesium Deficiency / congenital*
  • Magnesium Deficiency / genetics
  • Molecular Sequence Data
  • Mutation, Missense*
  • Nephrocalcinosis / genetics*
  • Polydipsia / genetics
  • Polyuria / genetics
  • Rickets / genetics
  • Sequence Homology, Amino Acid

Substances

  • CLDN19 protein, human
  • Claudins

Supplementary concepts

  • Hypomagnesemia 1, Intestinal