先天性肾源性尿崩症

1、Diseases Associated with G protein-Coupled ReceptorsGiving By wangnisha Xiexixiu Zhangwenshan Wangjing brief introduction The human genome may encode as many as 2000 different GPCRs. Their importance in human biology is reflected by the fact that more than one-quarter of all prescription drugs act a

2、s ligands that bind to this huge superfamily of receptors. A number of inherited disorders have been traced to defects in both GPCRs and heterotrimeric G protein . Several diseasesCongenital nephrogenic diabetes insipidus (CNDI) Congenital nephrogenic diabetes insipidus (CNDI) is a rare inherited di

3、sease in which infants suffer serious dehydration as the result of an inability of their kidneys to produce a concentrated urine. If not diagnosed promptly, the chronic dehydration can produce mental retardation, inadequate growth, and even death. CNDI 先天性肾源性尿崩症疾病属性疾病属性：罕见的遗传性疾病主要症状主要症状： 由于肾脏集合管对抗利尿

4、激素不起反应而致尿浓缩障碍，出现多饮、多尿和尿比重降低。 患病的婴儿的肾脏缺乏产生终尿的能力，他们会遭受到严重的脱水。如果没有及时地诊断治疗，这种慢性的的脱水会引发智障碍、生长迟缓、甚至是死亡.病理检查病理检查：抗利尿激素受体发生错误造成信号传导问题，导致CNDI肾脏的细胞失去了对抗利尿激素的应答能力.1The cause of the diseaseresult from mutations in aquaporins, The water channels of the plasma membrane.The cause of the disease图示为肾脏的水通道蛋白(Aquapori

5、n-2)，这是一个六次跨膜的蛋白质，氮末端和碳末端都在膜内，有三个细胞外环和两个细胞内环。图上的黑点表示突变位点，这些突变位点的变化导致水通道蛋白的失活或通透性增强，相应表现为病人脱水或不排尿。相应于CNDI的突变为Q57P Other reasons In most case ,however, the fault lies in the vasopressin(后叶升压素，即抗利尿素) receptor, which is typically shortened as the result of a mutation that introduces a stop codon into th

6、e mRNA, causing premature termination of polypeptide synthesis . A different type of debilitating mutation in this same GPCR leads to an amino acid substitution at the junction between the third transmembrane segment and the second intracellular loop .Even though this receptor can still bind vasopressin at its external surface, the receptor cannot activate the G protein and thus cannot pass the signal downstream to the effector.12.3New discovery in koreaHer mother and her father are not suffered from this disease.The girls disease was thought to be an autosomal recessive form. Ala (GCC) t