Universidad de la Republica, Uruguay.
Am J Med Genet C Semin Med Genet. 2009 Nov 15;151C(4):263-80. doi: 10.1002/ajmg.c.30227.
Motile cilia have long been known to play a role in processes such as cell locomotion and fluid movement whereas the functions of primary cilia have remained obscure until recent years. To date, ciliary dysfunction has been shown to be causally linked to a number of clinical manifestations that characterize the group of human disorders known as ciliopathies. This classification reflects a common or shared cellular basis and implies that it is possible to associate a series of different human conditions with ciliary dysfunction, which allows gaining insight into the cellular defect in disorders of unknown etiology solely based on phenotypic observations. Furthermore, to date we know that the cilium participates in a number of biological processes ranging from chemo- and mechanosensation to the transduction of a growing list of paracrine signaling cascades that are critical for the development and maintenance of different tissues and organs. Consequently, the primary cilium has been identified as a key structure necessary to regulate and maintain cellular and tissue homeostasis and thus its study is providing significant information to understand the pathogenesis of the different phenotypes that characterize these human conditions. Finally, the similarities between different ciliopathies at the phenotypic level are proving to be due to their shared cellular defect and also their common genetic basis. To this end, recent studies are showing that mutations in a given ciliary gene often appear involved in the pathogenesis of more than one clinical entity, complicating their genetic dissection, and hindering our ability to generate accurate genotype-phenotype correlations.
纤毛在细胞运动和液体流动等过程中起着重要作用，而初级纤毛的功能直到近年来才变得模糊。迄今为止，纤毛功能障碍已被证明与许多临床症状有关，这些症状构成了一组被称为纤毛病的人类疾病。这种分类反映了共同的细胞基础，并意味着可以将一系列不同的人类疾病与纤毛功能障碍联系起来，这使得仅基于表型观察就可以深入了解未知病因疾病的细胞缺陷。此外，迄今为止，我们知道纤毛参与了许多生物学过程，从化学和机械感觉到越来越多的旁分泌信号转导途径的转导，这些过程对不同组织和器官的发育和维持至关重要。因此，初级纤毛已被确定为调节和维持细胞和组织内稳态的关键结构，因此对其研究为理解这些人类疾病的不同表型的发病机制提供了重要信息。最后，不同纤毛病在表型水平上的相似性被证明是由于它们共同的细胞缺陷和共同的遗传基础。为此，最近的研究表明，特定纤毛基因的突变通常与一种以上的临床实体的发病机制有关，这使得它们的遗传分析变得复杂，并阻碍了我们生成准确的基因型-表型相关性的能力。
