Boucher Catherine, Sandford Richard
Department of Medical Genetics, Cambridge Institute for Medical Research, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2XY, UK.
Eur J Hum Genet. 2004 May;12(5):347-54. doi: 10.1038/sj.ejhg.5201162.
Autosomal dominant polycystic kidney disease (ADPKD) is a common inherited nephropathy affecting over 1:1000 of the worldwide population. It is a systemic condition with frequent hepatic and cardiovascular manifestations in addition to the progressive development of renal cysts that eventually result in loss of renal function in the majority of affected individuals. The diagnosis of ADPKD is typically made using renal imaging despite the identification of mutations in PKD1 and PKD2 that account for virtually all cases. Mutations in PKD1 are associated with more severe clinical disease and earlier onset of renal failure. Most PKD gene mutations are loss of function and a 'two-hit' mechanism has been demonstrated underlying focal cyst formation. The protein products of the PKD genes, the polycystins, form a calcium-permeable ion channel complex that regulates the cell cycle and the function of the renal primary cilium. Abnormal cilial function is now thought to be the primary defect in several types of PKD including autosomal recessive polycystic kidney disease and represents a novel and exciting mechanism underlying a range of human diseases.
常染色体显性多囊肾病（ADPKD）是一种常见的遗传性肾病，全球发病率超过千分之一。它是一种全身性疾病，除了肾囊肿进行性发展最终导致大多数患者肾功能丧失外，还常伴有肝脏和心血管表现。尽管已鉴定出几乎所有病例中涉及的PKD1和PKD2突变，但ADPKD的诊断通常仍采用肾脏成像方法。PKD1突变与更严重的临床疾病和肾衰竭的早期发作相关。大多数PKD基因突变是功能丧失性突变，并且已经证明“两次打击”机制是局灶性囊肿形成的基础。PKD基因的蛋白质产物多囊蛋白形成一种钙通透性离子通道复合物，调节细胞周期和肾初级纤毛的功能。现在认为，包括常染色体隐性多囊肾病在内的几种类型的PKD的主要缺陷是纤毛功能异常，这代表了一系列人类疾病的一种新颖且令人兴奋的潜在机制。
