Primary Ciliary Dyskinesia and Overlapping Syndromes

描述(由申请人提供)： 原发性纤毛运动障碍(PCD)是一种常染色体隐性遗传性疾病，导致粘液球菌清除障碍，以反复支气管炎、鼻-鼻窦炎、中耳炎和发展为支气管扩张症为特征。在这种疾病中，运动纤毛由9对外部微管和1对中央微管组成，大多数患者表现为动力蛋白臂缺陷，其他患者表现为轴线组件缺陷或纤毛超微结构正常。在过去的10年里，在理解潜在的缺陷、识别导致PCD的特定基因突变以及确定患有PCD的患者的自然临床病程方面取得了很大进展。到目前为止，有三个基因(DNAI1、DNAH11和DNAH5)具有“严重”(功能丧失)突变，在30%的PCD患者中是致病的。尽管最近有了这些进展，但诊断仍然很困难，这种疾病经常得不到诊断。运动性纤毛病与其他(“原发”/“感觉性”)非运动性综合征重叠的谱系也正在确定，这些情况对临床表现的影响尚不清楚。描述最佳治疗方法的证据很少，甚至没有证据。这次会议的目标将是为国际专家提供机会，以建立一个工作组，以实现以下四个目标：(1)通过诊断测试的标准化来优化PCD的诊断；(2)通过全球网络来定义PCD基因和基因突变；(3)优化对PCD患者的临床护理，并发展临床研究网络，以通过临床试验测试疗法；以及(4)完善纤毛疾病的命名并更好地确定重叠特征。 公共卫生相关性： 原发性纤毛运动障碍是一种运动纤毛的遗传性疾病，会导致复发性支气管炎、慢性鼻窦炎和支气管扩张或不可逆转的呼吸道损伤。这些表现的发生是因为纤毛不能有效地将粘液移出呼吸道。在过去的10年里，在理解这种疾病的基本病理生理学以及临床病程的自然历史方面取得了很大的进展。还开发了有助于诊断这种疾病的改进工具，并确定了重叠症状。鉴于这些发展，应该建立一个正式的国际工作组，以加强合作，并为临床试验网络提供机会。可以建立初级纤毛运动障碍中心来促进这一过程。由美国国立卫生研究院赞助的一次会议将启动这些重要举措。

DESCRIPTION (provided by applicant): Primary ciliary dyskinesia (PCD), an autosomal recessive disorder leading to impaired mucocociliary clearance, is characterized by recurrent bronchitis, rhinosinusitis, otitis media and development of bronchiectasis. In this disease, the motile cilia, which consists of a configuration of nine outer microtubule pairs and a central pair, exhibit defective dynein arms in most patients, and others exhibit defective axonemal components or have normal ciliary ultrastructure. Over the past 10 years, much progress has occurred in understanding the underlying defect, in identifying specific genetic mutations leading to PCD, and in defining the natural clinical course of patients afflicted with the disorder. To date, three genes (DNAI1, DNAH11, and DNAH5) with "severe" (loss-of-function) mutations are disease-causing in 30% of patients with PCD. Despite these recent developments, diagnosis remains difficult and the disease often goes unrecognized. The spectrum of motile ciliopathies overlapping with other ("primary"/"sensory") non-motile syndromes is also being identified, and the impact of these conditions on clinical manifestations is poorly understood. There is minimal to no evidence describing best treatment practices. The objectives of this conference will be to provide an opportunity for international experts to establish a working group to meet the following four objectives: (1) To optimize diagnosis of PCD through standardization of diagnostic testing; (2) To define PCD genes and gene mutations through global networking; (3) To optimize clinical care of PCD patients and develop clinical research networks to test therapies through clinical trials; and (4) To refine nomenclature for ciliopathies and better define overlapping features. PUBLIC HEALTH RELEVANCE: Primary ciliary dyskinesia, a genetic disorder of the motile cilia, leads to recurrent bronchitis, chronic rhinosinusitis and bronchiectasis or irreversible airway damage. These manifestations occur because the cilia are not effective at moving mucous out of the airways. Over the past 10 years, much progress has occurred in understanding the underlying pathophysiology of this disease as well as the natural history of the clinical course. Improved tools that help in diagnosing the disease have also been developed and overlapping syndromes have been identified. Given these developments, a formal international working group should be established to improve collaborations as well as provide an opportunity for a clinical trial network. Primary ciliary dyskinesia centers of excellence could be established to facilitate this process. A NIH-sponsored conference would launch these important initiatives.