Badano Jose L, Mitsuma Norimasa, Beales Phil L, Katsanis Nicholas
McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University, Baltimore, Maryland 21205, USA.
Annu Rev Genomics Hum Genet. 2006;7:125-48. doi: 10.1146/annurev.genom.7.080505.115610.
Cilia and flagella are ancient, evolutionarily conserved organelles that project from cell surfaces to perform diverse biological roles, including whole-cell locomotion; movement of fluid; chemo-, mechano-, and photosensation; and sexual reproduction. Consistent with their stringent evolutionary conservation, defects in cilia are associated with a range of human diseases, such as primary ciliary dyskinesia, hydrocephalus, polycystic liver and kidney disease, and some forms of retinal degeneration. Recent evidence indicates that ciliary defects can lead to a broader set of developmental and adult phenotypes, with mutations in ciliary proteins now associated with nephronophthisis, Bardet-Biedl syndrome, Alstrom syndrome, and Meckel-Gruber syndrome. The molecular data linking seemingly unrelated clinical entities are beginning to highlight a common theme, where defects in ciliary structure and function can lead to a predictable phenotypic pattern that has potentially predictive and therapeutic value.
纤毛和鞭毛是古老的、在进化上保守的细胞器，它们从细胞表面伸出以执行多种生物学功能，包括全细胞运动、液体流动、化学感受、机械感受和光感受以及有性生殖。与其严格的进化保守性一致，纤毛缺陷与一系列人类疾病相关，如原发性纤毛运动障碍、脑积水、多囊肝和多囊肾病以及某些形式的视网膜变性。最近的证据表明，纤毛缺陷可导致更广泛的发育和成人表型，现在纤毛蛋白的突变与肾单位肾痨、巴德-比德尔综合征、阿尔斯特伦综合征和梅克尔-格鲁伯综合征相关。将看似不相关的临床实体联系起来的分子数据开始凸显一个共同主题，即纤毛结构和功能的缺陷可导致一种具有潜在预测和治疗价值的可预测表型模式。
