先天性腎源性尿崩癥

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 先天性腎源性尿崩癥疾病屬性疾病屬性：罕見的遺傳性疾病主要癥狀主要癥狀： 由于腎臟集合管對(duì)抗利尿

4、激素不起反應(yīng)而致尿濃縮障礙，出現(xiàn)多飲、多尿和尿比重降低。 患病的嬰兒的腎臟缺乏產(chǎn)生終尿的能力，他們會(huì)遭受到嚴(yán)重的脫水。如果沒有及時(shí)地診斷治療，這種慢性的的脫水會(huì)引發(fā)智障礙、生長(zhǎng)遲緩、甚至是死亡.病理檢查病理檢查：抗利尿激素受體發(fā)生錯(cuò)誤造成信號(hào)傳導(dǎo)問題，導(dǎo)致CNDI腎臟的細(xì)胞失去了對(duì)抗利尿激素的應(yīng)答能力.1The cause of the diseaseresult from mutations in aquaporins, The water channels of the plasma membrane.The cause of the disease圖示為腎臟的水通道蛋白(Aquapori

5、n-2)，這是一個(gè)六次跨膜的蛋白質(zhì)，氮末端和碳末端都在膜內(nèi)，有三個(gè)細(xì)胞外環(huán)和兩個(gè)細(xì)胞內(nèi)環(huán)。圖上的黑點(diǎn)表示突變位點(diǎn)，這些突變位點(diǎn)的變化導(dǎo)致水通道蛋白的失活或通透性增強(qiáng)，相應(yīng)表現(xiàn)為病人脫水或不排尿。相應(yīng)于CNDI的突變?yōu)镼57P Other reasons In most case ,however, the fault lies in the vasopressin(后葉升壓素，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