Primary ciliary dyskinesia (PCD), an inherited motile ciliopathy, is characterised by recurrent upper and lower respiratory tract infections, organ laterality defects, subfertility and neonatal respiratory distress due to impaired ciliary function.1 Over 50 PCD disease-causing genes have been identified that impact the structure and function of the cilia (figure 1, originally in Despotes et al 1). Significant clinical heterogeneity is associated with PCD, in part driven by genotype; genotype–phenotype relationships are an emerging area of great importance within this rare disease.2–4 However, clinical heterogeneity has also been reported among patients with the same genetic variants,3 suggesting that genetic modifiers may play an important role in disease manifestations. In their Thorax paper, Pifferi and colleagues have helped uncover our incomplete understanding of this heterogeneity by evaluating the impact of TAS2R38 polymorphisms within specific PCD genotypes. The authors specifically explored the impact of these polymorphisms on Pseudomonas aeruginosa (PA) infections, lung function and nasal nitric oxide (nNO) levels.5 Figure 1 : The location and function of the 54 currently known disease-causing genes implicated in PCD, originally published in Despotes et al (1). Panel A: Respiratory Epithelial Cell. * DNAH9 and DNAH11 are represented twice (panel A and panel C) as these genes are important in ODA structure at different locations along the axoneme length, as demonstrated in panel A. Panel B: Cilium and Intraflageller Transport. Panel C: Axoneme (in cross-section). The outer doublet A and B microtubules are labeled. The cross-section of the axoneme shows the “9 + …

中文翻译：

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增加了原发性纤毛运动障碍中基因型-表型关系的复杂性：TAS2R38作为基因修饰剂


原发性纤毛运动障碍 （PCD） 是一种遗传性运动纤毛病，其特征是反复发作的上下呼吸道感染、器官偏侧性缺陷、不孕症低下和由于纤毛功能受损而导致的新生儿呼吸窘迫。已鉴定出 50 多个影响纤毛结构和功能的 PCD 致病基因（图 1，最初来自 Despotes 等人 1）。显著的临床异质性与 PCD 相关，部分由基因型驱动;基因型-表型关系是这种罕见疾病中非常重要的新兴领域2-4。然而，在具有相同遗传变异的患者中也报道了临床异质性，3 这表明遗传修饰因子可能在疾病表现中发挥重要作用。在他们的 Thorax 论文中，Pifferi 及其同事通过评估特定 PCD 基因型中 TAS2R38 多态性的影响，帮助揭示了我们对这种异质性的不完整理解。作者专门探讨了这些多态性对铜绿假单胞菌 （PA） 感染、肺功能和鼻腔一氧化氮 （nNO） 水平的影响。图 1：目前已知的 54 个与 PCD 有关的致病基因的位置和功能，最初发表在 Despotes 等人 （1） 上。图 A：呼吸道上皮细胞。* DNAH9 和 DNAH11 有两次表示（图 A 和图 C），因为这些基因在轴丝长度不同位置的 ODA 结构中很重要，如图 A 所示。图 B：纤毛和鞭毛内运输。图 C：轴丝（横截面）。外部双峰 A 和 B 微管被标记。轴丝的横截面显示“9 + ...