PURPOSE Ciliopathies are highly heterogeneous clinical disorders of the primary cilium. We aim to characterize a large cohort of ciliopathies phenotypically and molecularly. METHODS Detailed phenotypic and genomic analysis of patients with ciliopathies, and functional characterization of novel candidate genes. RESULTS In this study, we describe 125 families with ciliopathies and show that deleterious variants in previously reported genes, including cryptic splicing variants, account for 87% of cases. Additionally, we further support a number of previously reported candidate genes (BBIP1, MAPKBP1, PDE6D, and WDPCP), and propose nine novel candidate genes (CCDC67, CCDC96, CCDC172, CEP295, FAM166B, LRRC34, TMEM17, TTC6, and TTC23), three of which (LRRC34, TTC6, and TTC23) are supported by functional assays that we performed on available patient-derived fibroblasts. From a phenotypic perspective, we expand the phenomenon of allelism that characterizes ciliopathies by describing novel associations including WDR19-related Stargardt disease and SCLT1- and CEP164-related Bardet-Biedl syndrome. CONCLUSION In this cohort of phenotypically and molecularly characterized ciliopathies, we draw important lessons that inform the clinical management and the diagnostics of this class of disorders as well as their basic biology.

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纤毛病的病态基因组：更新。

目的 纤毛病是原发性纤毛的高度异质性临床疾病。我们的目标是从表型和分子上表征一大群纤毛病。方法 纤毛病患者的详细表型和基因组分析，以及新候选基因的功能表征。结果 在这项研究中，我们描述了 125 个纤毛病家族，并表明先前报道的基因中的有害变异，包括神秘的剪接变异，占病例的 87%。此外，我们进一步支持了一些先前报道的候选基因（BBIP1、MAPKBP1、PDE6D 和 WDPCP），并提出了九个新的候选基因（CCDC67、CCDC96、CCDC172、CEP295、FAM166B、LRRC34、TMEM17、TTC6 和 TTC23），其中三个（LRRC34、TTC6、和 TTC23）得到了我们对可用的患者来源的成纤维细胞进行的功能分析的支持。从表型的角度来看，我们通过描述新的关联（包括 WDR19 相关的 Stargardt 病和 SCLT1 和 CEP164 相关的 Bardet-Biedl 综合征）来扩展表征纤毛病的等位基因现象。结论 在这一具有表型和分子特征的纤毛病队列中，我们吸取了重要的经验教训，为此类疾病的临床管理和诊断及其基础生物学提供信息。