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.
|Effective start/end date||7/1/10 → 6/30/11|
- National Institutes of Health: $15,000.00
Inborn Genetic Diseases