Primary Ciliary Dyskinesia (PCD) via the CCNO Gene

Primary Ciliary Dyskinesia (PCD) is a genetic disorder affecting the function of motile cilia (Leigh et al. 2009). The hallmark features of PCD are neonatal respiratory distress, chronic coughing, and recurrent sinus and/or ear infections; 80-100% of all PCD patients have one or more of these symptoms. In 20-50% of individuals with PCD, the major visceral organs are reversed from their normal positions (also called situs inversus) (Sutherland and Ware 2009). Kartagener’s syndrome is a condition defined by the symptomatic triad of situs inversus, sinusitis and bronchiectasis. Patients with PCD can also have abnormal orientation of some organs but not others (a condition called situs ambiguus or heterotaxy) (Kennedy et al. 2007). For more information, see GeneReviews (Zariwala et al. 2013).

Primary Ciliary Dyskinesia is inherited most commonly in an autosomal recessive manner due to defects in motile cilia. To date, defects in at least 30 genes, including CCNO, have been reported to cause PCD (Wallmeier 2014; Casey 2015). CCNO is required for mother centriole generation and migration. Individuals with biallelic pathogenic variants in CCNO have recurrent upper and lower respiratory infections, resulting in bronchiectasis which can lead to lung failure (Wallmeier 2014). Affected individuals have an absence or decreased number of cilia. The majority of reported pathogenic variants are chain terminating variants (nonsense, frameshift), but some missense variants have also been reported to be pathogenic (Wallmeier 2014; Casey 2015). All affected individuals reported to date had situs solitus, suggesting that CCNO, unlike most PCD-associated genes, is not involved in the establishment of left/right asymmetry (Wallmeier 2014).

Ten out of 54 presumably unrelated individuals with an absence or decreased number of cilia were found to have biallelic pathogenic variants in CCNO (Wallmeier et al. 2014). This corresponds to <1% of all PCD cases (Zariwala et al. 2013).

This test provides full coverage of all coding exons of the CCNO gene plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define full coverage as >20X NGS reads or Sanger sequencing. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).