Unravelling genetic and clinical phenotype correlations in primary ciliary dyskinesia: a cohort study

<bold>Background:</bold> Primary ciliary dyskinesia (PCD) is a rare, genetically heterogeneous disorder that leads to a wide range of clinical manifestations. <bold>Aim:</bold> To describe the clinical features and genetic test results of 23 Slovenian patients with PCD, investigating correlations between genetic variants and clinical phenotypes. <bold>Methods:</bold> Clinical records and genetic analysis of 23 patients (median age 18.5 years, range 7 months – 27.1 years) with PCD were reviewed. <bold>Results:</bold> The study revealed a median age of diagnosis at 5.5 years, with a high prevalence of chronic rhinitis (96%), chronic wet cough (91%), chronic otitis media (97%), situs inversus (35%), and a history of neonatal respiratory distress (55%). The mean FEV1 was 88% (Z-score -1.01). The average lung clearance index (LCI) was 10.4 in 11 evaluated patients. Genetic analysis identified biallelic variants in 22 patients and a single mutation in 1 patient across 11 PCD-associated genes, with DNAH5 (n=5), DNAH11 (n=5) and SPAG1 (n=3) being the most commonly affected genes. Other genes harboring variants included DNAAF1, DRC1, DNAI1, ODAD1, ODAD4, MCIDAS, HYDIN, and RSPH4A. Eight new pathogenic and likely pathogenic variants were identified. Patients with DNAH11 mutations had more severe upper airway symptoms, fewer lower airway symptoms, and better lung function and were diagnosed at an older age than those with DNAH5 mutations. However, the differences were not statistically significant. <bold>Conclusion:</bold> This study underscores PCD's clinical and genetic heterogeneity, offering insights into potential genotype-phenotype correlations. With an increase in the size of the genetic analysis, clearer genotype-phenotype correlations may emerge.