title: Two novel genotypes of the thiazide-sensitive Na-Cl cotransporter (SLC12A3) gene in patients with Gitelman's syndrome.
abstract: 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.
authors.affiliation: Division of Nephrology and Endocrinology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Aoi
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Nakayama
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Tahira
authors.forename: Akira
authors.initials: A
authors.lastname: Haketa
authors.forename: Minako
authors.initials: M
authors.lastname: Yabuki
authors.forename: Tadataka
authors.initials: T
authors.lastname: Sekiyama
authors.forename: Chie
authors.initials: C
authors.lastname: Nakane
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Mano
authors.forename: Hideomi
authors.initials: H
authors.lastname: Kawachi
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Sato
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Soma
authors.forename: Kouichi
authors.initials: K
authors.lastname: Matsumoto
mesh_terms: 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
chemical_list: D011955:Receptors, Drug; C578874:SLC12A3 protein, human; D049992:Sodium Chloride Symporters; D064486:Solute Carrier Family 12, Member 3; D027981:Symporters; C064415:thiazide receptor