Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
Department of Pediatrics, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia.
Genet Med. 2020 Jun;22(6):1051-1060. doi: 10.1038/s41436-020-0761-1. Epub 2020 Feb 14.
Ciliopathies are highly heterogeneous clinical disorders of the primary cilium. We aim to characterize a large cohort of ciliopathies phenotypically and molecularly.
Detailed phenotypic and genomic analysis of patients with ciliopathies, and functional characterization of novel candidate genes.
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.
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.
纤毛病是原发性纤毛的高度异质性临床疾病。我们旨在从表型和分子上对一大组纤毛病患者进行特征描述。
对纤毛病患者进行详细的表型和基因组分析，并对新的候选基因进行功能特征描述。
在这项研究中，我们描述了 125 个纤毛病家系，并表明以前报道的基因中的有害变异，包括隐匿剪接变异，占病例的 87%。此外，我们进一步支持了一些以前报道的候选基因（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）通过我们对可用的患者衍生成纤维细胞进行的功能检测得到了支持。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，扩展了纤毛病的等位基因现象。
在这个经过表型和分子特征描述的纤毛病队列中，我们得出了重要的结论，这些结论为这类疾病的临床管理和诊断以及它们的基础生物学提供了信息。
