Pollak M R, Delaney V B, Graham R M, Hebert S C
Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
J Am Soc Nephrol. 1996 Oct;7(10):2244-8. doi: 10.1681/ASN.V7102244.
A defect in distal renal tubular sodium chloride handling is thought to be responsible for the clinical phenotype of Gitelman's syndrome, a variant of Bartter's syndrome. To study the possible involvement of the renal thiazide-sensitive NaCl cotransporter gene in the syndrome, a linkage analysis study in the largest reported kindred with the syndrome was performed. A human homolog of rat thiazide-sensitive cotransporter was cloned and mapped to chromosome 16q13 by fluorescent in situ hybridization. All 17 family members in two generations were genotyped at loci in this region. There were no recombinants observed between the Gitelman's syndrome phenotype and inheritance of D16S408 alleles, yielding a lod score of 3.88 at Q = 0. By contrast, recombinants were observed between Gitelman's syndrome and the flanking markers D16S419 and D16S400, localizing the responsible gene in this family to a 15 centimorgan region on chromosome 16q. These genetic data, together with current understanding of the molecular physiology of the thiazide-sensitive cotransporter, are strong evidence that the latter is defective in this kindred with Gitelman's syndrome.
远曲肾小管对氯化钠处理存在缺陷被认为是吉特曼综合征（巴特综合征的一种变异型）临床表型的病因。为研究肾噻嗪敏感型氯化钠共转运体基因在该综合征中可能的作用，对已报道的最大的患有该综合征的家系进行了连锁分析研究。通过荧光原位杂交技术克隆了大鼠噻嗪敏感型共转运体的人类同源物，并将其定位到16号染色体q13区。对该区域的位点进行基因分型，测定了这两代人中所有17名家庭成员的基因类型。在吉特曼综合征表型与D16S408等位基因的遗传之间未观察到重组，在Q = 0时获得的对数优势分数为3.88。相比之下，在吉特曼综合征与侧翼标记D16S419和D16S400之间观察到了重组，将该家系中的致病基因定位到16号染色体q区的一个15厘摩区域。这些遗传数据，连同目前对噻嗪敏感型共转运体分子生理学的了解，有力地证明了在这个患有吉特曼综合征的家系中，后者存在缺陷。
