Wolf Matthias T F
Division of Pediatric Nephrology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Curr Opin Pediatr. 2015 Apr;27(2):201-11. doi: 10.1097/MOP.0000000000000194.
Nephronophthisis (NPHP) is an autosomal recessive cystic kidney disease and is one of the most common genetic disorders causing end-stage renal disease (ESRD) in children and adolescents. NPHP is a genetically heterogenous disorder with 20 identified genes. NPHP occurs as an isolated kidney disease, but approximately 15% of NPHP patients have additional extrarenal symptoms affecting other organs [e.g. eyes, liver, bones and central nervous system (CNS)]. The pleiotropy in NPHP is explained by the finding that almost all NPHP gene products share expression in primary cilia, a sensory organelle present in most mammalian cells. If extrarenal symptoms are present in addition to NPHP, these disorders are classified as NPHP-related ciliopathies (NPHP-RC). This review provides an update about recent advances in the field of NPHP-RC.
The identification of novel disease-causing genes has improved our understanding of the pathomechanisms contributing to NPHP-RC. Multiple interactions between different NPHP-RC gene products have been published and outline the interconnectivity of the affected proteins and shared pathways.
The significance of recently identified genes for NPHP-RC is discussed and the complex role and interaction of NPHP proteins in ciliary function and cellular signalling pathways is highlighted.
肾单位肾痨（NPHP）是一种常染色体隐性遗传性囊性肾病，是导致儿童和青少年终末期肾病（ESRD）的最常见遗传疾病之一。NPHP是一种具有20个已确定基因的遗传异质性疾病。NPHP作为一种孤立的肾脏疾病出现，但约15%的NPHP患者有影响其他器官（如眼睛、肝脏、骨骼和中枢神经系统（CNS））的额外肾外症状。NPHP中的多效性可通过以下发现来解释：几乎所有NPHP基因产物在初级纤毛中共同表达，初级纤毛是大多数哺乳动物细胞中存在的一种感觉细胞器。如果除了NPHP还存在肾外症状，这些疾病则被归类为NPHP相关纤毛病（NPHP-RC）。本综述提供了关于NPHP-RC领域近期进展的最新信息。
新致病基因的鉴定增进了我们对导致NPHP-RC发病机制的理解。不同NPHP-RC基因产物之间的多种相互作用已被发表，概述了受影响蛋白质的相互联系和共享途径。
讨论了近期鉴定的基因对NPHP-RC的意义，并强调了NPHP蛋白在纤毛功能和细胞信号通路中的复杂作用及相互作用。
