Genetics of Primary Ciliary Dyskinesia

Sponsor

University of North Carolina, Chapel Hill (Other)

Overall Status

Completed

CT.gov ID

NCT02389049

Collaborator

Rare Diseases Clinical Research Network (Other), National Institutes of Health (NIH) (NIH), National Heart, Lung, and Blood Institute (NHLBI) (NIH)

320

Enrollment

Locations

40.9

Duration (Months)

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Primary Ciliary Dyskinesia Kartagener Syndrome

Detailed Description

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.

Study Design

Study Type:

Observational

Actual Enrollment :

320 participants

Observational Model:

Cohort

Time Perspective:

Cross-Sectional

Official Title:

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

Study Start Date :

Feb 1, 2015

Actual Primary Completion Date :

Jul 1, 2018

Actual Study Completion Date :

Jul 1, 2018

Outcome Measures

Primary Outcome Measures

Confirm PCD diagnosis in patients using a panel of 32 genes [Up to 5 years]
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.

Secondary Outcome Measures

Identify patients with PCD who do not have a biallelic PCD-causing mutation [Up to 5 years]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Stanford University	Palo Alto	California	United States	94304
2	The Children's Hospital, Denver	Aurora	Colorado	United States	80045
3	Riley Hospital for Children	Indianapolis	Indiana	United States	46202
4	Washington University, St. Louis	Saint Louis	Missouri	United States	63110
5	The University of North Carolina at Chapel Hill	Chapel Hill	North Carolina	United States	27599
6	Children's Hospital and Regional Medical Center, Seattle	Seattle	Washington	United States	98105
7	The Hospital for Sick Children	Toronto	Ontario	Canada
8	McGill University	Montreal	Quebec	Canada