Lemmink H H, van den Heuvel L P, van Dijk H A, Merkx G F, Smilde T J, Taschner P E, Monnens L A, Hebert S C, Knoers N V
Department of Pediatrics, University of Nijmegen, The Netherlands.
Pediatr Nephrol. 1996 Aug;10(4):403-7. doi: 10.1007/s004670050129.
Gitelman syndrome is a mostly autosomal recessive disorder affecting the renal tubular function associated with hypokalemia and hypomagnesemia. Functional studies point to a defect in the distal renal tubule in the thiazide-sensitive, electroneutral sodium-chloride co-transporter (TSC). Based upon the localization of a 2.6 cDNA encoding the human TSC to chromosome 16q13, polymorphic markers spanning the region from 16p12 to 16q21 were tested for linkage to the Gitelman syndrome locus in three Dutch families with autosomal recessive inheritance of this disorder. Using two-point linkage analysis, a maximum LOD score (Zmax of 4.49 (at theta = 0.00) was found for the marker D16S408. One crucial recombination event places the Gitelman syndrome locus distal to D16S419 at 16q12-13. Subsequently we have tested our group of Gitelman patients for mutations in the human TSC gene. Two mutations were identified in three Gitelman families. Our study confirms that the human TSC gene is involved in Gitelman syndrome. Patients from three Gitelman families reveal two identical human TSC mutations, suggesting these families share a common ancestor.
吉特林综合征是一种主要为常染色体隐性遗传的疾病，会影响肾小管功能，伴有低钾血症和低镁血症。功能研究表明，在噻嗪类敏感的电中性氯化钠共转运体（TSC）中，远端肾小管存在缺陷。基于编码人类TSC的2.6 cDNA定位于16号染色体q13区，对跨越16p12至16q21区域的多态性标记进行了检测，以确定其与三个患有该疾病常染色体隐性遗传的荷兰家庭中吉特林综合征基因座的连锁关系。使用两点连锁分析，发现标记D16S408的最大LOD分数（Zmax为4.49，在θ=0.00时）。一个关键的重组事件将吉特林综合征基因座定位在16q12 - 13处的D16S419远端。随后，我们对我们的吉特林患者群体进行了人类TSC基因突变检测。在三个吉特林家庭中鉴定出两个突变。我们的研究证实人类TSC基因与吉特林综合征有关。来自三个吉特林家庭的患者显示出两个相同的人类TSC突变，表明这些家庭有共同的祖先。
