Quantitative High Speed Video Profiling Discriminates Between Variants of Primary Ciliary Dyskinesia

Primary ciliary dyskinesia (PCD) is a genetically heterogeneous condition. The number of genes associated with primary ciliary dyskinesia is rising, and the link between genotype and clinical phenotype is largely unknown (1). Recent advances in molecular genotyping have helped establish the association between genetic defects and aberrant cilia ultrastructure in PCD, as detected by transmission electron microscopy. However, up to 30% of PCD cases do not show any specific ultrastructural defects and thus cannot be detected using this method. A classic example of this occurs in PCD cases caused by mutations in the DNAH11 (dynein axonemal heavy chain 1) protein, where aberrant ciliary beating can be detected via high-speed video microscopy (HSVM) analysis, but no ultrastructural defect is observed (2, 3). Even in cases where ultrastructural defects do exist, they can be difficult to detect using standard transmission electron microscopy techniques, and therefore patients who harbor such subtle defects are at risk of being misdiagnosed. PCD caused by mutations in the protein HYDIN, for example, display normal ciliary beat frequency and rarely exhibit abnormal ciliary transmission electron microscopy, yet mucociliary clearance is compromised.