Genotypes and associations with symptoms in primary ciliary dyskinesia

Abstract Background Knowledge about genotype-phenotype associations is crucial for understanding the clinical variability of primary ciliary dyskinesia (PCD). We studied how feasible it is to collect information about causative genes directly from people with PCD through questionnaires, and investigated associations between clinical characteristics, symptoms, and genotype. Methods We used data from the anonymous international participatory cohort COVID-PCD, set up in 2020 to follow people with PCD during the COVID-19 pandemic. A baseline questionnaire asked genetic test results, clinical characteristics, and current symptoms. We grouped reported causative genes into categories based on associated defects and studied differences between groups. Results Among the 759 COVID-PCD study participants, 444 (58%) reported genetic testing, and of these, 289 (65%) reported that a gene was identified. We included 206 who knew and reported a causative gene. The most common genes were DNAH5 (n=71; 34%), DNAH11 (n=27; 13%), CCDC40 (n=21; 10%), DNAI1 (n=18; 9%), CCDC39 (n=13; 6%), and RSPH1 (n=8; 4%). The dynein structure (DS) group was the largest (n=127) followed by the nexin-dynein regulatory complex (ND-RC) group (n=38), dynein assembly (DA) group (n=21), and radial spoke and central complex (RS-CC, n=20) Current age and sex were similar across groups; but median age at diagnosis was markedly higher in the RS-CC group (11 years) compared to 4–7 years in the other groups (p=0.035). Laterality defects were reported by one person (5%) in RS-CC group, compared with 37%-60% in other groups (p=0.001). Overall, symptoms were frequently reported by participants in all 4 groups with little difference between groups. Conclusion Our results confirmed known differences in laterality defects and congenital heart disease between genotypes and showed frequent upper and lower respiratory symptoms in all groups regardless of reported gene.