Primary ciliary dyskinesia in Volendam: Diagnostic and phenotypic features in patients with a CCDC114 mutation

Abstract

Primary ciliary dyskinesia (PCD) is a heterogeneous disease, with impaired mucociliary clearance causing respiratory tract infections. A founding CCDC114 mutation has led to a relatively homogeneous and large Dutch PCD population in Volendam. Our aim was to describe their phenotype. Therefore, all Volendam PCD patients seen at the Amsterdam UMC were included in this study. Data were collected on lung function, microbiology, radiology, and ear-nose-throat (ENT) symptoms. A mixed effects model estimated lung function decline in %point per year (95% confidence interval [CI]). Thirty-three (60%) out of approximately 56 Volendam PCD patients were treated at our center and included in this study. Only 30% of patients had situs inversus. FEV 1 declined in children (À1.43%/year, CI: À1.80/À1.05), but not in adults (0.01%/year, CI: À0.36/0.38). Pseudomonas aeruginosa was cultured in 21% of children and 60% of adults, respectively. Patients who have been infected at some point with P. aeruginosa had a steeper decline in FEV 1 as compared to patients that have never been infected. Neonatal symptoms (79%) and ENT problems (94%) were common; fertility issues however, were not (11%) common. Compared to other PCD cohorts, the Volendam/CCDC114 patients have a moderately severe phenotype with lung function decline predominantly occurring in childhood.

ODAD1 variants resulting from splice-site mutations retain partial function and cause primary ciliary dyskinesia with outer dynein arm defects

“…Previously, all researchers except Ostrowski et al (2022) have used NM_144577 in studies on ODAD1 (Knowles et al, 2013;Onoufriadis et al, 2013;Li et al, 2019;Chen et al, 2020;Guo et al, 2020;Guan et al, 2021;Hannah et al, 2022;Kos et al, 2022). In this study, NM_ 001364171 was detected in bronchial mucosa biopsy samples and peripheral blood cells collected from patient Ⅲ: 1 and control individuals (Supplementary Figure S2).…”

Estimates of primary ciliary dyskinesia prevalence: a scoping review

“…The large variation in the prevalence estimates may be, in part, due to differences in the geographical regions and time periods when the studies were conducted, as this would impact the study population and case definitions. For example, the estimated prevalence may be higher [30] in geographical regions that have isolated communities, founder mutations or higher rates of consanguinity [25,27] (e.g., RSPH4A in Puerto Rico [31,32], CCDC114 in Volendam [33] or DNAH5 variant in Amish communities [34]). Additionally, over time the case definition for PCD has evolved from a syndrome (e.g., Kartagener's syndrome) to confirmatory diagnostic testing.…”

Primary Ciliary Dyskinesia: A Clinical Review

“…A recent description of novel RSPH4A variants in unrelated Chinese families, however, noted abnormal sperm morphology; two female patients were also infertile, perhaps related to abnormalities in motile cilia of the fallopian tubes [ 184 ]. Although ODAD1 is expressed in the human testis, it does not appear to be crucial for sperm function and may be compensated by other genes (such as CCDC36 ), so fertility is less affected [ 88 , 185 ]. Conversely, although DNAH17 is essential for the ODA in the sperm axoneme it is not required for the respiratory cilia axoneme, resulting in isolated male infertility without PCD [ 186 ].…”