Takeuchi K, Kure S, Kato T, Taniyama Y, Takahashi N, Ikeda Y, Abe T, Narisawa K, Muramatsu Y, Abe K
Second Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
J Clin Endocrinol Metab. 1996 Dec;81(12):4496-9. doi: 10.1210/jcem.81.12.8954067.
Gitelman's syndrome is a variant of Bartter's syndrome, characterized by hypokalemia, hypomagnesemia, hypocalciuria, and hypovolemia. We have observed familial cases of Gitelman's syndrome, and a possible mutation in thiazide-sensitive Na-Cl cotransporter was investigated in this kindred. The proband was a 47-yr-old Japanese female, and her mother was also affected. Her parents and maternal grandparents are consanguineous. By using PCR-amplification and direct sequencing, we identified a novel non-conservative missense mutation at 623 amino acid position, which substitutes proline for leucine (L623P), and also creates an Nci I restriction site in the exon 15. The mutation was not detected in normal healthy subjects (n = 102). Nci I digestion of PCR-amplified exon 15 DNA fragments from individuals in the family indicated the autosomal recessive inheritance of the disorder. In conclusion, the L623P mutation in the thiazide-sensitive Na-Cl cotransporter gene is suggested to impair the transporter activity, and to underlie this familial Gitelman's syndrome; Gitelman's syndrome observed in this kindred has been inherited in an autosomal recessive fashion.
吉特曼综合征是巴特综合征的一种变异型，其特征为低钾血症、低镁血症、低钙尿症和血容量减少。我们观察到了吉特曼综合征的家族病例，并对该家系中噻嗪类敏感型钠 - 氯共转运体可能存在的突变进行了研究。先证者是一名47岁的日本女性，她的母亲也患有该病。她的父母及外祖父母均为近亲结婚。通过聚合酶链反应（PCR）扩增和直接测序，我们在第623个氨基酸位置发现了一个新的非保守错义突变，该突变使亮氨酸被脯氨酸替代（L623P），并且在第15外显子中产生了一个Nci I限制性酶切位点。在102名正常健康受试者中未检测到该突变。对该家族中个体的PCR扩增第15外显子DNA片段进行Nci I酶切，表明该疾病为常染色体隐性遗传。总之，噻嗪类敏感型钠 - 氯共转运体基因中的L623P突变可能损害了转运体活性，并成为这个家族性吉特曼综合征的病因；在这个家系中观察到的吉特曼综合征是以常染色体隐性方式遗传的。
