Genetics of Primary Ciliary Dyskinesia

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.

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.