Association of a mutation in thiazide-sensitive Na-Cl cotransporter with familial Gitelman's syndrome

J Clin Endocrinol Metab. 1996 Dec;81(12):4496-9. doi: 10.1210/jcem.81.12.8954067.

Abstract

Gitelman's syndrome is a variant of Bartter's syndrome, characterized by hypokalemia, hypomagnesemia, hypocalciuria, and hypovolemia. We have observed familial cases of Gitelman's syndrome, and a possible mutation in thiazide-sensitive Na-Cl cotransporter was investigated in this kindred. The proband was a 47-yr-old Japanese female, and her mother was also affected. Her parents and maternal grandparents are consanguineous. By using PCR-amplification and direct sequencing, we identified a novel non-conservative missense mutation at 623 amino acid position, which substitutes proline for leucine (L623P), and also creates an Nci I restriction site in the exon 15. The mutation was not detected in normal healthy subjects (n = 102). Nci I digestion of PCR-amplified exon 15 DNA fragments from individuals in the family indicated the autosomal recessive inheritance of the disorder. In conclusion, the L623P mutation in the thiazide-sensitive Na-Cl cotransporter gene is suggested to impair the transporter activity, and to underlie this familial Gitelman's syndrome; Gitelman's syndrome observed in this kindred has been inherited in an autosomal recessive fashion.

Publication types

  • Case Reports

MeSH terms

  • Bartter Syndrome / genetics*
  • Benzothiadiazines*
  • Carrier Proteins / genetics*
  • Diuretics
  • Female
  • Humans
  • Middle Aged
  • Mutation*
  • Sodium / metabolism
  • Sodium Chloride Symporter Inhibitors / pharmacology*
  • Sodium Chloride Symporters
  • Symporters*

Substances

  • Benzothiadiazines
  • Carrier Proteins
  • Diuretics
  • Sodium Chloride Symporter Inhibitors
  • Sodium Chloride Symporters
  • Symporters
  • Sodium