Parfrey P S
Division of Nephrology, Memorial University of Newfoundland, St. John's, Canada.
Curr Opin Nephrol Hypertens. 1993 Mar;2(2):192-200. doi: 10.1097/00041552-199303000-00004.
Huge strides have been made in the molecular genetics and clinical investigation of several inherited renal diseases. In autosomal dominant polycystic kidney disease 1) the genetic localization of the defective gene that causes type 1 disease has been narrowed to 500 to 750 kb on chromosome 16; 2) cystogenesis has been associated with increased cell proliferation, continuing cyst secretion, and a defect in cell polarity; however, the mechanisms by which the genetic defects in autosomal dominant polycystic kidney disease translate into cyst formation are unknown; 3) activation of the renin system has been reported as an important potential cause of hypertension; and 4) factors that influence the progression to renal failure have been identified. In Alport's syndrome, mutations in the alpha 5 (IV) collagen gene on the X chromosome have been demonstrated that may induce defective assembly of alpha 3 (IV) chains by an unknown mechanism, which leads to the disruption of the glomerular basement membrane. In diabetic nephropathy, it has been suggested that familial factors, perhaps genetic in origin, may play an important role in its development.
在几种遗传性肾脏疾病的分子遗传学和临床研究方面已经取得了巨大进展。在常染色体显性多囊肾病中：1）导致1型疾病的缺陷基因的遗传定位已缩小到16号染色体上500至750千碱基对的区域；2）囊肿形成与细胞增殖增加、囊肿持续分泌以及细胞极性缺陷有关；然而，常染色体显性多囊肾病中的基因缺陷转化为囊肿形成的机制尚不清楚；3）肾素系统的激活已被报道为高血压的一个重要潜在原因；4）已经确定了影响肾衰竭进展的因素。在阿尔波特综合征中，已证实X染色体上的α5（IV）胶原基因突变可能通过未知机制诱导α3（IV）链组装缺陷，从而导致肾小球基底膜破坏。在糖尿病肾病中，有人提出家族因素，可能起源于遗传，可能在其发展中起重要作用。
