Two novel genotypes of the thiazide-sensitive Na-Cl cotransporter (SLC12A3) gene in patients with Gitelman's syndrome.
Gitelman's syndrome is an autosomal recessive disorder marked by salt wasting and hypokalaemia resulting from loss-of-function mutations in the SLC12A3 gene that codes for the thiazide-sensitive Na-Cl cotransporter. Gitelman's syndrome is usually distinguished from Bartter's syndrome by the presence of both hypomagnesaemia and hypocalciuria. Although recent advances in molecular genetics may make it possible to both diagnose and differentiate these diseases, the phenotypes sometimes overlap. Here we report two sporadic cases of Gitelman's syndrome and two novel genotypes of SLC12A3. Patient 1 was a compound heterozygote with a known missense mutation, L849H, and a novel mutation, R852H in exon 22. Patient 2 was homozygous for the missense mutation L849H. To our knowledge, this is the first report of a patient homozygous for 849H. Interestingly, both patients were affected with autoimmune thyroid disease. Patient 1 was affected with Hashimoto's disease, and Patient 2 was affected with Graves' disease. The symptoms of Patient 2 were more serious than those of Patient 1. Although the patients both carried the 849H allele (Patient 1 as a heterozygote and Patient 2 as a homozygous), their clinical symptoms differed. The difference in the clinical features may have been due both to phenotypic differences and the fact that Gitelman's syndrome is a complicated disorder.
Aoi
Noriko
N
Division of Nephrology and Endocrinology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan.
Nakayama
Tomohiro
T
Tahira
Yoshiko
Y
Haketa
Akira
A
Yabuki
Minako
M
Sekiyama
Tadataka
T
Nakane
Chie
C
Mano
Hiroaki
H
Kawachi
Hideomi
H
Sato
Naoyuki
N
Soma
Masayoshi
M
Matsumoto
Kouichi
K
D000328:Adult; D001483:Base Sequence; D004252:DNA Mutational Analysis; D005260:Female; D005838:Genotype; D053579:Gitelman Syndrome / Q000150:complications / Q000235:genetics*; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D011955:Receptors, Drug / Q000235:genetics*; D049992:Sodium Chloride Symporters / Q000235:genetics*; D064486:Solute Carrier Family 12, Member 3; D027981:Symporters / Q000235:genetics*; D013967:Thyroiditis, Autoimmune / Q000150:complications / Q000235:genetics
D011955:Receptors, Drug; C578874:SLC12A3 protein, human; D049992:Sodium Chloride Symporters; D064486:Solute Carrier Family 12, Member 3; D027981:Symporters; C064415:thiazide receptor