Nakayama Tomohiro, Aoi Noriko, Sato Naoyuki, Sato Mikano, Kosuge Kotoko, Izumi Yoichi, Soma Masayoshi, Matsumoto Koichi
Division of Laboratory Medicine, Department of Pathology and Microbiology, Nihon University School of Medicine, Itabashi-ku, Tokyo 173-8610, Japan.
Rinsho Byori. 2010 Feb;58(2):156-61.
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.
吉特曼综合征是一种常染色体隐性疾病，其特征为盐耗竭和低钾血症，这是由编码噻嗪类敏感型钠 - 氯共转运蛋白的SLC12A3基因功能丧失性突变所致。吉特曼综合征通常通过低镁血症和低钙尿症的存在与巴特综合征相区分。人类SLC12A3基因位于16号染色体上，由26个外显子组成，编码一种蛋白质，该蛋白质含有12个假定的跨膜结构域，其氨基末端和羧基末端位于细胞内且较长。在本研究中，我们开发了一种使用DNA测序诊断吉特曼综合征的基因诊断方法。一名患者被发现是复合杂合子，其22号外显子的核苷酸2552处有一个单碱基替换（CTC突变为CAC，L849H）以及核苷酸2561处有一个替换（CGC突变为CAC，R852H）。家系连锁分析证实849H是父本等位基因，852H是母本等位基因。该方法可以节省时间和成本，并且对每家医院的临床实验室进行基因检测应该是有用的。
