Association of a mutation in thiazide-sensitive Na-Cl cotransporter with familial Gitelman's syndrome.
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.
Takeuchi
K
K
Second Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
Kure
S
S
Kato
T
T
Taniyama
Y
Y
Takahashi
N
N
Ikeda
Y
Y
Abe
T
T
Narisawa
K
K
Muramatsu
Y
Y
Abe
K
K
D001477:Bartter Syndrome / Q000235:genetics*; D001581:Benzothiadiazines; D002352:Carrier Proteins / Q000235:genetics*; D004232:Diuretics; D005260:Female; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D012964:Sodium / Q000378:metabolism; D049993:Sodium Chloride Symporter Inhibitors / Q000494:pharmacology*; D049992:Sodium Chloride Symporters; D027981:Symporters
D001581:Benzothiadiazines; D002352:Carrier Proteins; D004232:Diuretics; D049993:Sodium Chloride Symporter Inhibitors; D049992:Sodium Chloride Symporters; D027981:Symporters; D012964:Sodium