Genetics of Primary Ciliary Dyskinesia

Study Overview
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Brief Summary
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This study is designed to study DNA sequencings for mutations in a research genetic test panel of genes (which contains all 32 known and/or published genes associated with PCD). The study aims to show that about 70% of PCD patients have biallelic mutations in one of these genes. This project will enroll patients who have already had a clinical evaluation, and have clinical features consistent with PCD.

Detailed Description
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The investigators have established a Consortium of 9 geographically-dispersed clinical research sites to study rare disease of the airways, including Primary Ciliary Dyskinesia (PCD). PCD is a genetic disorder with defective mucociliary clearance (MCC), sinus and pulmonary disease with chronic infection, and organs located on the wrong side of the body in about 50% of patients (Kartagener Syndrome). Lung disease occurs early in children with PCD, but establishing a diagnosis remains a major challenge, based on the traditional approaches of using electron microscopy and/or ciliary waveform analysis to define abnormalities of ciliary ultrastructure and/or function. For this study, blood or buccal samples for DNA will be collected and genetic testing in patients with known or suspected PCD will be performed. This study can include term neonates with respiratory distress of unknown etiology and features of PCD, particular laterality defects (situs inversus or heterotaxy). The key hypothesis for this study is that a genetic test panel of 32 genes will confirm a diagnosis in most patients with PCD.

Official Title
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Research Genetic Testing for Primary Ciliary Dyskinesia Using a Panel of Genes

Conditions
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Primary Ciliary Dyskinesia, Kartagener Syndrome

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Any patient who has ≥ 2 clinical features (+/- lab) characteristic of PCD, including: Neonatal respiratory distress after term (or near-term) birth and/or laterality defect ( situs inversus or heterotaxy) and/or daily wet cough before 6 months of age and/or middle ear disease and/or chronic nasal congestion before 6 months of age and/or bronchiectasis and/or male infertility due to sperm tail dysfunction and/or low nasal nitric oxide levels (<77 nanoliters/minute) and/or defective ciliary ultrastructure Exclusion Criteria: Known diagnosis of cystic fibrosis with classic clinical presentation and elevated sweat chloride levels and/or two known disease-causing Cystic Fibrosis transmembrane conductance regulator (CFTR) mutations, or documented primary or acquired immunodeficiency. Known explanation for bronchiectasis (and other clinical features), such as α1-antitrypsin deficiency (ZZ or ZS), inflammatory bowel disease or rheumatoid arthritis. Any patient who is unwilling or unable to provide consent or to comply with the testing required in this protocol A participant should not be in the study if they have not had a standard clinical evaluation to address other potential causes of chronic oto-sino- pulmonary disease.
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Confirm PCD diagnosis in patients using a panel of 32 genes | The primary objective is to perform research genetic (Ampliseq panel) testing in patients who are known or suspected to have PCD, based on previous research or future clinical and lab characterization by certified clinical research sites. We will define the prevalence of biallelic PCD-causing mutations in patients who fulfill criteria of very high likelihood of PCD, as well as prevalence in other patients with some features of PCD. We anticipate successful completion of this objective will provide the foundation for development of clinically available genetic test panels, particularly as additional PCD genes are identified. | Up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Identify patients with PCD who do not have a biallelic PCD-causing mutation | The secondary objective is to perform research genetic testing to identify patients with PCD who do not have biallelic PCD-causing mutations in known PCD genes, so they can be exome sequenced to discover novel genes associated with PCD. We anticipate that successful completion of this objective will enable the development of more extensive genetic test panels that are more robust to diagnose PCD. | Up to 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Primary Ciliary Dyskinesia, Kartagener Syndrome