Genetic Testing for PCD: The Basics

There are known PCD-causing mutations on two genes linked to the production of outer dynein arm (ODA) protein: DNAI1 and DNAH5). Together, the mutations on these two genes account for approximately 38% of all cases of PCD and close to 63% of ODArelated PCD. Current clinical genetic testing is limited to these known mutations. For this reason, clinicians who are interested in ordering a clinical genetic test for PCD should contact Ambry Genetics or the UNC Molecular Genetics Laboratory prior to ordering the test.

Interpreting the Results

Because PCD is a recessive disorder, genetic confirmation of the diagnosis requires positive identification of two known PCD mutations. When two mutations are identified, there is high specificity for a diagnosis of PCD. However, a negative result or a result positive for only a single mutation does not rule-out a diagnosis of PCD, nor does it suggest that a clinical diagnosis of PCD is incorrect. Individuals may harbor disease causing mutations not yet identified, therefore not detectable with current genetic panels. In this case, patients and their physicians may want to explore ongoing research studies which are seeking to identify additional disease causing mutations in these and possibly other genes. It is very important that genetic testing be part of a comprehensive clinical evaluation.*

Who Should Consider Genetic Testing?*

Ambry Genetics PCD Panel 61™ suggests that clinical genetic testing for PCD is appropriate for the following indications:

• Known or suspected PCD
• Chronic sinusitis or bronchiectasis not due to cystic fibrosis
• Suspected PCD with heterotaxy, situs ambiguus, or situs inversus (aka Kartagener syndrome)
• Congenital heart defect associated with recurrent respiratory disease or heterotaxy
• Chronic otitis media with effusion
• Male infertility with other signs of PCD
• Idiopathic respiratory distress in full-term neonates
• Carrier status determination for relatives of patients with known mutations

The decision to pursue genetic testing cannot be taken lightly. Interpretation of inconclusive results and access to genetic counseling regardless of the results, are factors to be considered before making the decision. Both Ambry Genetics and the UNC Molecular Genetics Laboratory are committed to working with patients and clinicians to ensure that appropriate candidates for testing are identified and that necessary follow-up is available to patients and ordering clinicians. For more information and contacts, please visit the following sites or contact the PCD Foundation:

University of North Carolina, Chapel Hill, Molecular Genetics Laboratory:
http://www.pathology.unc.edu/common/weck.htm
http://www.unchealthcare.org/site/labs/forms/dnah5

Ambry Genetics PCD Panel 61™:
http://www.ambrygen.com/clinical_diagnostic_and_carrier_testing/test_PCD_61.asp