Hildebrandt F, Omram H
University Children's Hospital, Freiburg, Germany.
Pediatr Nephrol. 2001 Feb;16(2):168-76. doi: 10.1007/s004670000518.
Nephronophthisis (NPH) and medullary cystic kidney disease (MCKD) constitute a group of renal cystic diseases, which share a common characteristic renal histologic triad of tubular basement membrane disintegration, tubular atrophy with cyst development, and interstitial cell infiltration with fibrosis. The different disease variants lead to chronic renal failure with onset at characteristic age ranges for recessive NPH and dominant MCKD. There is extensive gene locus heterogeneity with at least three different loci for nephronophthisis (NPHP1, NPHP2, and NPHP3) and two different loci for MCKD (MCKD1 and MCKD2). Juvenile nephronophthisis, in addition, can be associated with extrarenal organ involvement. We have identified by positional cloning the gene (NPHP1) for juvenile nephronophthisis (NPH1), as a first step towards understanding the pathogenesis of this disease group. Its gene product, nephrocystin, is a novel protein, which contains a src-homology 3 (SH3) domain. We put forward a hypothesis that the pathogenesis of NPH might be related to signaling processes at focal adhesions (the contact points between cells and extracellular matrix) and/or adherens junctions (the contact points between cells).
肾单位肾痨（NPH）和髓质囊性肾病（MCKD）构成一组肾囊性疾病，它们具有共同的特征性肾脏组织学三联征，即肾小管基底膜崩解、肾小管萎缩伴囊肿形成，以及间质细胞浸润伴纤维化。不同的疾病变体导致慢性肾衰竭，隐性NPH和显性MCKD在特定年龄范围发病。存在广泛的基因座异质性，肾单位肾痨至少有三个不同的基因座（NPHP1、NPHP2和NPHP3），髓质囊性肾病有两个不同的基因座（MCKD1和MCKD2）。此外，青少年肾单位肾痨可伴有肾外器官受累。我们通过定位克隆确定了青少年肾单位肾痨（NPH1）的基因（NPHP1），这是了解该疾病组发病机制的第一步。其基因产物肾囊肿蛋白是一种新型蛋白质，含有一个src同源3（SH3）结构域。我们提出一个假说，即NPH的发病机制可能与粘着斑（细胞与细胞外基质之间的接触点）和/或黏着连接（细胞之间的接触点）处的信号传导过程有关。
