Selected studies reporting phenotype-genotype associations among patients with primary ciliary dyskinesia (PCD)
| Study | Study design, country, data collection period, time followed up | Inclusion criteria, age | N | Main findings |
| Shoemark [1] | • Retrospective, cross-sectional • UK, the Netherlands, France • Collected until 2019 | • People with genetically confirmed PCD • Median age 11 years (IQR 4–18 years) | 396 | • Genotype groups: 171 (43%) dynein structure defect (most frequent: DNAH5), 94 (24%) dynein assembly defect (most frequent: CCDC103), 50 (13%) radial spoke/central complex defect (most frequent: RSPH4A), 68 (17%) N-DRC/molecular ruler (most frequent: CCDC39), 13 other defects • N-DRC or molecular ruler defects associated with poor FEV1 (−2.7 z-scores, sd 1.6) and absence of history of rhinitis • Dynein structure defects associated with preserved lung function (−1.4 FEV1 z-scores, sd 1.4) and absence of NRDS |
| Pifferi [24] | • Prospective, longitudinal • Italy • Collected 2008–2018 • Prospective, longitudinal • Mean follow-up 5 years (range 1–10 years) | • People aged >5 years with confirmed PCD • 66 children enrolled, mean±sd age 10±4 years • 69 adults enrolled, mean±sd age 34±11 years | 135 | • 131 with TEM results: 33 (25%) had ODA/IDA, 33 (25%) had IDA/CA/MTD, 14 (11%) had CA, 25 (19%) had ODA only, 26 (20%) had normal TEM • Children: BMI lowest in those with CA defect (−0.76 z-score, sd 2.09); lung function worst in those with IDA/CA/MTD (FEV1 z-scores −1.29, sd 0.82) or CA alone (FEV1 z-scores −1.62, sd 1.02) • Adults: worst lung function in those with IDA/CA/MTD defects (FEV1 z-scores −3.72, sd 1.28) • Genotype comparisons: worst lung function among those with CCDC39 and CCDC40 (FEV1 z-scores −1.38, sd 0.78) |
| Davis [18] | • Prospective, longitudinal • USA, Canada • Collected 2006–2011 • Median follow-up 6 years (range 1–6 years) | • People aged <19 years with confirmed PCD • Mean±sd age at enrolment 8±5 years | 137 | • 55 (40%) had ODA defects, 20 (15%) had ODA+IDA defects, 41 (30%) had IDA/CA/MTD defects, 12 (9%) had normal ultrastructure, 9 (6%) had other defects • CCDC39 and CCDC40 mutations (IDA/CA/MTD defects) associated with lower FEV1 (−15% predicted) and weight (−0.8 z-scores) and height (−0.60 z-scores) than DNAH5 (ODA defects) • Lung function decline (FEV1) was highest among those with IDA/CA/MTD defects |
| Halbeisen [21] | • Retrospective, cross-sectional • 14 different countries • Collected until 2016 | • People aged >5 years • Definite, probable, or clinical PCD diagnosis | 991 | • 689 with TEM results: 425 (43%) had ODA or IDA, 134 (14%) had MT defects, 123 were non-diagnostic • Patients with MT defects had worse lung function (−1.91 FEV1 z-scores, −1.08 FVC z-scores than patients with non-diagnostic TEM (−1.19 FEV1 z-scores, −0.74 FVC z-scores and patient with ODA or IDA defects (−1.50 FEV1 z-scores, −0.73 FVC z-scores) |
| Shah [25] | • Retrospective, longitudinal • UK • Data period: 1980–2014 • Median follow-up 7 years (range 1–34 years) | • People aged >17 years with confirmed PCD • Median age 35 years (range 19–75 years) | 151 | • 138 with TEM results: 92 (67%) had IDA and/or ODA defects, 27 (20%) had MTD defects, 19 (13%) had normal/inconclusive result • Greatest annual FEV1 decline in patients MTD defects (−0.75% predicted, 95% CI −2.08–0.58) compared with ODA/IDA (−51% predicted, 95% CI −1.41–0.39) and normal/inconclusive TEM (−0.13% predicted, 95%CI −1.53–1.28) |
| Davis [26] | • Prospective, longitudinal • USA, Canada • Collected 2006–2012 | • People aged <19 years with confirmed PCD • Median age 8 years (range 5–11 years) | 118 | • 54 (46%) had ODA defects, 18 (15%) had ODA+IDA defects, 40 (34%) had IDA/CA/MTD defects, 6 (5%) had CA or IDA only • Patients with IDA/CA/MTD defects had worse lung function (72% predicted FEV1, IQR 58–88), more radiographic disease (3.5 lobes with bronchiectasis), and poorer growth (BMI 46th percentile) than those with ODA or ODA+IDA |
IQR: interquartile range; N-DRC: nexin-dynein regulatory complex; FEV1: forced expiratory volume in the first second; NRDS: neonatal respiratory distress; ODA; outer dynein arm; IDA: inner dynein arm; CA: central apparatus; MTD: microtubular disorganisation; BMI: body mass index; TEM: transmission electron microscopy; MT: microtubular; FVC: forced vital capacity.