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常染色体显性遗传型多囊肾病(ADPKD)是一种十分常见的遗传病,发病率为1‰,我国目前约有150万患者。其临床表现为多发性肾脏囊肿、持续性高血压和泌尿系感染等症状,由于缺乏有效治疗手段,多数患者发展为终末期肾衰而不得不进行肾脏替代治疗或肾移植手术。目前已知ADPKD的主要致病基因有Ⅰ型和Ⅱ型多囊肾致病基因(PKD1和PKD2),分别占ADPKD患者的85%和15％。其中PKD1位于人16p13．3,基因长52 kb,含46个外显子;PKD2位于人4q21-23,基因长68 kb,含15个外显子,但具体致病机制仍不清楚。虽然未对ADPKD表型进行临床分型,但患者间存在明显的表型差异,其中起病早(平均约30-40岁左右)、症状重(导致终末期肾衰平均年龄约53岁)的患者多由PKD1突变引发;而较晚起病(平均约60岁左右)、症状较轻(导致终末期肾衰平均年龄约69岁)的患者多与PKD2突变有关,故与PKD1相关的研究更为人瞩目。
Autosomal dominant polycystic kidney disease (ADPKD) is a very common genetic disease, the incidence rate of 1 ‰, China currently has about 1.5 million patients. The clinical manifestations of multiple renal cysts, persistent hypertension and urinary tract infection and other symptoms, due to the lack of effective treatment, the majority of patients with end-stage renal failure and had to undergo renal replacement therapy or kidney transplant surgery. It is known that the main pathogenic genes of ADPKD are type 1 and type 2 polycystic kidney disease gene (PKD1 and PKD2), accounting for 85% and 15% of ADPKD patients, respectively. Among them, PKD1 is located in human 16p13.3, with a gene length of 52 kb and 46 exons. PKD2 is located in human 4q21-23 with a length of 68 kb and contains 15 exons. However, the exact pathogenesis of PKD1 remains unclear. Although the ADPKD phenotype was not clinically subdivided, there were significant phenotypic differences among patients with early onset (around 30-40 on average) and severe symptoms (leading to an average terminal age of 53 years) Patients are mostly caused by mutations in PKD1; and patients with later onset (average about 60 years) and mild symptoms (average age of about 69 years leading to end-stage renal failure) are associated with PKD2 mutations, so PKD1-related studies People attention.