Nephronophthisis and related syndromes.
Nephronophthisis and related syndromes.
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DOI：
10.1097/mop.0000000000000194
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发表时间：
2015-04
影响因子：
3.6
通讯作者：
Wolf MT
中科院分区：
文献类型：
--
作者：
Wolf MT
肾病综合征（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）的最常见遗传性疾病之一。NPHP是一种遗传异质性疾病，具有20个已鉴定的基因。NPHP是一种孤立的肾脏疾病，但大约15%的NPHP患者有其他肾外症状，影响其他器官（如眼睛、肝脏、骨骼和CNS）。NPHP的多效性可以通过以下发现来解释：几乎所有的NPHP基因产物都在初级纤毛中表达，初级纤毛是大多数哺乳动物细胞中存在的感觉细胞器。如果除NPHP外还存在肾外症状，则这些疾病被归类为NPHP相关纤毛病（NPHP-RC）。本文就NPHP-RC的最新研究进展作一综述。新的致病基因的鉴定提高了我们对NPHP-RC病理机制的理解。不同NPHP-RC基因产物之间的多种相互作用已经发表，并概述了受影响的蛋白质和共享途径的互连性。最近发现的NPHP-RC基因的意义进行了讨论，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和相互作用。
Nephronophthisis (NPHP) represents 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 twenty identified genes. NPHP occurs as an isolated kidney disease but approxmiately 15% of NPHP patients have additional extrarenal symptoms affecting other organs (e.g. eyes, liver, bones, and 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 the recent advances in the field of NPHP-RC. The identification of novel disease-causing genes has improved our understanding of 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 signaling pathways is highlighted.