先天性肾源性尿崩症精品课件

Diseases Associated with G protein-Coupled Receptors Giving 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 as 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 diseases Congenital nephrogenic diabetes insipidus (CNDI) Congenital nephrogenic diabetes insipidus (CNDI) is a rare inherited disease 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：罕见的遗传性疾病 主要症状： 由于肾脏集合管对抗利尿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：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. 1 The cause of the disease result 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 (Aquaporin-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 the 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. 1 2.3 New discovery in korea Her mother and her father are not suffered from this disease. The girls disease was thought to be an autosomal recessive form. Ala (GCC) to Asp (GAC) in exon 1inherited form her father and Arg (CGC) to His (CAC) in exon 3 inherited from her mother. 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