Genotypes and associations with symptoms in primary ciliary dyskinesia

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 COVID19 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. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Protocols ### Funding Statement Our research was funded by the Swiss National Foundation (SNF 320030B\_192804/1), Switzerland, the Swiss Lung Association, Switzerland (2021-08\_Pedersen), and received support from the PCD Foundation, United States; the Verein Kartagener Syndrom und Primaere Ciliaere Dyskinesie, Germany; the PCD Support UK; and PCD Australia, Australia. M. Goutaki receives funding from the Swiss National Science Foundation (PZ00P3_185923). Study authors participate in the BEAT-PCD Clinical Research Collaboration, supported by the European Respiratory Society. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethical approval from the Cantonal Ethics Committee of Bern, Switzerland, Study ID: 2020-00830 I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors