Département de génétique, INSERM U 781, Université Paris Descartes-Sorbonne Paris Cité, Institut Imagine, Hôpital Necker Enfants Malades (AP-HP), 75015 Paris, France.
Am J Med Genet C Semin Med Genet. 2012 Aug 15;160C(3):165-74. doi: 10.1002/ajmg.c.31336. Epub 2012 Jul 12.
In the last 10 years, the primary cilia machinery has been implicated in more than a dozen disorders united as ciliopathies, including skeletal dysplasias, such as Jeune syndrome and short rib-polydactyly type III. Indeed, primary cilia play a vital role in transduction of signals in the hedgehog pathway that is especially important in skeletal development. In this review, we focus on skeletal conditions belonging to the ciliopathy group: the short rib-polydactyly group (SRPs) that includes Verma-Naumoff syndrome (SRP type III), Majewski syndrome (SRP type II), Jeune syndrome (ATD), as well as Ellis-van Creveld syndrome (EVC), the Sensenbrenner syndrome, and, finally, Weyers acrofacial dysostosis. Today, 10 different genes have been identified as responsible for seven "skeletal" ciliopathies. Mutations have been identified in dynein motor (DYNC2H1), in intraflagellar transport (IFT) complexes (IFT80, IFT122, IFT43, WDR35, WDR19, and TTC21B) as well as in genes responsible for the basal body (NEK1, EVC, and EVC2). The wide clinical variability observed for an individual ciliopathy gene supports the development of exome strategy specifically dedicated to cilia genes to identify mutations in this particularly heterogeneous group of disorders.
在过去的 10 年中，初级纤毛机械已涉及十多种疾病，这些疾病统称为纤毛病，包括骨骼发育不良，例如 Jeune 综合征和短肋-多指（趾）畸形 III 型。事实上，初级纤毛在 hedgehog 信号通路的信号转导中起着至关重要的作用，而 hedgehog 信号通路在骨骼发育中尤为重要。在这篇综述中，我们重点介绍属于纤毛病组的骨骼疾病：短肋-多指（趾）畸形组（SRPs），包括 Verma-Naumoff 综合征（SRP 型 III）、Majewski 综合征（SRP 型 II）、Jeune 综合征（ATD），以及 Ellis-van Creveld 综合征（EVC）、Sensenbrenner 综合征，最后是 Weyers 面-颅发育不良。如今，已有 10 个不同的基因被确定为 7 种“骨骼”纤毛病的致病基因。已经在动力蛋白（DYNC2H1）、内纤毛运输（IFT）复合物（IFT80、IFT122、IFT43、WDR35、WDR19 和 TTC21B）以及负责基底体的基因中发现了突变（NEK1、EVC 和 EVC2）。对于个体纤毛病基因观察到的广泛临床变异性支持外显子组策略的发展，该策略专门针对纤毛基因，以识别该特别异质疾病组中的突变。
