[Establishment of genetic testing for 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. The human SLC12A3 gene, which is located on chromosome 16, consists of 26 exons and encodes a protein that contains 12 putative transmembrane domains with long intracellular amino and carboxy termini. In the present study, we developed a method of genetic diagnosis for Gitelman's syndrome using DNA sequencing. A patient was found to be a compound heterozygote with a single base substitution at nucleotide 2552 (CTC-to-CAC, L849H) and a substitution at nucleotide 2561 (CGC-to-CAC, R852H) in exon 22. Familial linkage analysis confirmed that 849H was the paternal allele and 852H was the maternal allele. The method can save time and costs, and it should be useful for genetic testing in clinical laboratory of every hospital.
Nakayama
Tomohiro
T
Division of Laboratory Medicine, Department of Pathology and Microbiology, Nihon University School of Medicine, Itabashi-ku, Tokyo 173-8610, Japan. tnakayam@med.nihon-u.ac.jp
Aoi
Noriko
N
Sato
Naoyuki
N
Sato
Mikano
M
Kosuge
Kotoko
K
Izumi
Yoichi
Y
Soma
Masayoshi
M
Matsumoto
Koichi
K
D000483:Alleles; D002874:Chromosome Mapping; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics; D003362:Cost-Benefit Analysis; D005091:Exons / Q000235:genetics; D005820:Genetic Testing / Q000191:economics / Q000379:methods*; D053579:Gitelman Syndrome / Q000175:diagnosis* / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D009154:Mutation; D011955:Receptors, Drug / Q000235:genetics; D017422:Sequence Analysis, DNA; D049992:Sodium Chloride Symporters / Q000235:genetics; D064486:Solute Carrier Family 12, Member 3; D027981:Symporters / 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