Primary Ciliary Dyskinesia and Overlapping Syndromes

原发性纤毛运动障碍和重叠综合征

• 批准号: 8010351
• 负责人: Stephanie Duggins Davis
• 金额: $ 1.5万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8010351
• 关键词: Bronchiectasis; Bronchitis; Cilia; Clinical; Clinical Research; Clinical Trials; Clinical Trials Network; Collaborations; Defect; Development; Diagnosis; Diagnostic tests; Disease; Dynein ATPase; Exhibits; Functional disorder; Gene Mutation; Genes; Hereditary Disease; International; Microtubules; Mucous body substance; Natural History; Nomenclature; Otitis Media; Patients; Primary Ciliary Dyskinesias; Process; Recurrence; Sensory; Standardization; Syndrome; Testing; arm; chronic rhinosinusitis; clinical care; disease diagnosis; improved; loss of function mutation; meetings; public health relevance; rhinosinusitis; symposium; tool; working group

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.

描述（由申请人提供）： 原发性睫状运动障碍（PCD）是一种常染色体隐性疾病，导致粘膜钙切除率受损，其特征在于复发性支气管炎，鼻鼻炎，耳鼻喉介质和支气管扩张的发育。在这种疾病中，由九个外部微管对和中心对组成的纤毛纤毛在大多数患者中表现出有缺陷的动力蛋白臂，而其他则表现出缺陷的轴突成分或具有正常的纤毛超微结构。在过去的10年中，在理解潜在的缺陷，确定导致PCD的特定基因突变以及定义患有该疾病的患者的自然临床过程方面发生了很多进展。迄今为止，具有“严重”（功能丧失）突变的三个基因（DNAI1，DNAH11和DNAH5）在30％的PCD患者中引起疾病​​。尽管有这些最近的发展，但诊断仍然很困难，并且这种疾病常常无法识别。还可以鉴定出与其他（主要的“/“感觉”）非运动综合征重叠的运动纤维病的光谱，并且这些疾病对临床表现的影响知之甚少。没有描述最佳治疗方法的证据也不是最少。这次会议的目标是为国际专家提供一个工作组，以建立一个工作组来满足以下四个目标：（1）通过标准化诊断测试来优化PCD的诊断； （2）通过全球网络定义PCD基因和基因突变； （3）优化PCD患者的临床护理并开发通过临床试验测试疗法的临床研究网络； （4）用于完善纤毛病的命名法，并更好地定义重叠的特征。 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疾病，导致复发性支气管炎，慢性鼻孔炎和支气管张舒张或不可逆的气道损害。这些表现之所以发生，是因为纤毛在将粘液从气道中移出时无效。在过去的10年中，在理解该疾病的潜在病理生理以及临床病程的自然病史方面发生了很多进展。改进的有助于诊断疾病的工具也已经开发出来，并且已经确定了重叠的综合症。鉴于这些发展，应建立一个正式的国际工作组，以改善合作，并为临床试验网络提供机会。可以建立卓越的原发性睫状运动障碍中心，以促进这一过程。 NIH赞助的会议将启动这些重要的举措。