Axonemal Symmetry Break, a New Ultrastructural Diagnostic Tool for Primary Ciliary Dyskinesia?

Diagnosis testing for primary ciliary dyskinesia (PCD) requires a combination of investigations that includes study of ciliary beat pattern by high-speed video-microscopy, genetic testing and assessment of the ciliary ultrastructure by transmission electron microscopy (TEM). Historically, TEM was considered to be the “gold standard” for the diagnosis of PCD. However, with the advances in molecular genetic techniques, an increasing number of PCD variants show normal ultrastructure and cannot be diagnosed by TEM. During ultrastructural assessment of ciliary biopsies of patients with suspicion of PCD, we observed an axonemal defect not previously described that affects peripheral doublets tilting. To further characterize this defect of unknown significance, we studied the ciliary axonemes by TEM from both PCD-confirmed patients and patients with other sino-pulmonary diseases. We detected peripheral doublets tilting in all the PCD patients, without any significant difference in the distribution of ciliary beat pattern or mutated gene. This defect was also present in those patients with normal ultrastructure PCD subtypes. We believe that the performance of axonemal asymmetry analysis would be helpful to enhance diagnosis of PCD.

Psychological status of mothers of children with cystic fibrosis and primary ciliary dyskinesia

Objectives: We aimed to investigate depression, burnout, attitude, and burden of caregivers of children with cystic fibrosis (CF), and especially caregivers of children with primary ciliary dyskinesia (PCD) due to limited number of studies on this topic, and to compare them according to their children’s clinical status. Methods: Clinical features and demographic data of children and their families were asked to caregivers in four pediatric pulmonology centers. Beck Depression Inventory (BDI), Maslach Burnout Inventory (MBI), Zarit Caregiver Burden Scale (ZCBS), and Parental Attitude Research Instrument (PARI) were administered to caregivers in both groups. Results were compared between the two groups. Results: In total, 131 children with CF and 39 with PCD and their caregivers were involved in study. All primary caregivers were mothers in both groups. Depression, burnout, and burden scores of mothers of children with CF were significantly higher than mothers of children with PCD (p=0.017, p=0.024, p=0.038, respectively). Burnout was higher in both CF and PCD groups with low family income (p=0.022, p=0.034). Number of hospital visits in the previous six months was correlated with burnout in both CF and PCD groups (r=0.207, p=0.034; r=0.352, p=0.044). Conclusions: Although mothers of children with CF have higher depression, burnout, burden, and negative attitudes towards children than mothers of children with PCD, it is disregarded in mothers of children with PCD. Psychological problems of mothers of children with CF and PCD may increase with frequent hospital visits, hospitalizations, low family income, number of children, and chronic disease in another child.

Key Gene Network Related to Primary Ciliary Dyskinesia in Hippocampus of Patients with Alzheimer’S Disease Revealed by Weighted Gene Co-Expression Network Analysis

Background. Alzheimer's disease (AD) is closely related to aging, showing an increasing incidence rate for years. As one of the main organs involved in AD, hippocampus has been extensively studied due to its association with many human diseases. However, little knowledge is known on its association with primary ciliary dyskinesia (PCD). Material and Methods. The microarray data of hippocampus on AD were retrieved from the Gene Expression Omnibus (GEO) database to construct the co-expression network by weighted gene co-expression network analysis (WGCNA). The gene network modules associated with AD screened with the common genes were further annotated based on Gene Ontology (GO) database and enriched based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. The protein-protein interaction (PPI) network was constructed based on STRING database to identify the hub genes in the network. Results. Genes involved in PCD were identified in the hippocampus of AD patients. Functional analysis revealed that these genes were mainly enriched in ciliary tissue, ciliary assembly, axoneme assembly, ciliary movement, microtubule based process, microtubule based movement, organelle assembly, axoneme dynamin complex, cell projection tissue, and microtubule cytoskeleton tissue. A total of 20 central genes, e.g., DYNLRB2, ZMYND10, DRC1, DNAH5, WDR16, TTC25, and ARMC4 were identified as hub genes related to PCD in hippocampus of AD patients. Conclusion. Our study demonstrated that AD and PCD have shared metabolic pathways. These common pathways provide novel evidence for further investigation of the pathophysiological mechanism and the hub genes suggest new therapeutic targets for the diagnosis and treatment of AD and PCD. Subjects Bioinformatics, Cell Biology, Molecular Biology, Neurology

COVID-19 Vaccinations: Perceptions and Behaviours in People with Primary Ciliary Dyskinesia

Primary ciliary dyskinesia (PCD) is a rare genetic disease that causes recurrent respiratory infections. People with PCD may be at higher risk of severe coronavirus disease 2019 (COVID-19), and therefore vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is important. We studied vaccination willingness, speed of vaccination uptake, side effects, and changes in social contact behaviour after vaccination in people with PCD. We used data from COVID-PCD, an international participatory cohort study. A COVID-19 vaccination questionnaire was emailed to participants in May 2021 and 423 participants from 31 countries replied (median age: 30 years, range 1–85 years; 261 (62%) female). Vaccination uptake and willingness were high, with 273 of 287 adults (96%) being vaccinated or willing to be in June 2021; only 4% were hesitant. The most common reason for hesitancy was fear of side effects, reported by 88%. Mild side effects were common, but no participant reported severe side effects. Half of the participants changed their social behaviour after vaccination by seeing friends and family more often. The high vaccination willingness in the study population might reflect the extraordinary effort taken by PCD support groups to inform people about COVID-19 vaccination. Clear and specific information and involvement of representatives is important for high vaccine uptake.

Respiratory symptoms of Swiss people with Primary Ciliary Dyskinesia

Background: Mostly derived from chart reviews, where symptoms are recorded in a nonstandardised manner, clinical data about primary ciliary dyskinesia (PCD) are inconsistent, which leads to missing and unreliable information. We assessed the prevalence and frequency of respiratory symptoms and studied differences by age and sex among an unselected population of Swiss people with PCD. Methods: We sent a questionnaire that included items from the FOLLOW–PCD standardised questionnaire to all Swiss PCD registry participants. Results: We received questionnaires from 74 out of 86 (86%) invited persons or their caregivers (age range: 3–73 years; median age: 23), including 68% adults (≥18 years) and 51% females. Among participants, 70 (94%) reported chronic nasal symptoms, most frequently runny nose (65%), blocked nose (55%), or anosmia (38%). Ear pain and hearing problems were reported by 58% of the participants. Almost all (99%) reported cough and sputum production. The most common chronic cough complications were gastroesophageal reflux (n=11; 15%), vomiting (n=8; 11%), and urinary incontinence (n=6; 8%). Only 9 participants (12%) reported frequent wheeze, which occurred mainly during infection or exercise, while 49 persons (66%) reported shortness of breath; 9% even at rest or during daily activities. Older patients reported more frequent nasal symptoms and shortness of breath. We found no difference by sex or ultrastructural ciliary defect. Conclusion: This is the first study that describes patient–reported PCD symptoms. The consistent collection of standardised clinical data will allow us to better characterise the phenotypic variability of the disease and study disease course and prognosis.

Report of the 2021 Primary ciliary dyskinesia foundation annual meeting

In August 2021, the Primary Ciliary Dyskinesia (PCD) Foundation hosted a 2-day international virtual conference designed to share discoveries in PCD genetics, cilia biology, and clinical research and care. The conference was organized around the theme of building a community for clinical research. This article provides a report of the proceedings.