Primary ciliary dyskinesia multigene NGS diagnostic testing in Cyprus

The dataset describes the genetic diagnosis in the national PCD
cohort of Cyprus, an island with a high disease prevalence. Targeted
next-generation sequencing (NGS) of 39 known PCD genes was
carried out in samples from 48 patients of Greek-Cypriot and other
ancestries. Molecular diagnosis was achived in 74% of the unrelated
families tested (68% of Greek-Cypriot and 90% of non-Greek-Cypriot origin
respectively). A total of 24 different mutations in 11 genes, 12
of which are novel were identified. These were categorized as
nonsense (n= 9), splice-site (7), frameshift (n= 4), and missense (n= 3)
mutations, and small deletions (n= 1). Homozygosity was more common in
Greek-Cypriot than non-Greek-Cypriot patients (88% vs 46.2%, p =0.016).
Four mutations (DNAH11:c.5095-2A>G, CFAP300:c.95_103delGCCGGCTCC,
TTC25:c.716G>A, RSPH9: c.670+2T>C,) were found in 74% of the
diagnosed Greek-Cypriot families, usually appearing in homozygosity and
regional clusters. Patients with RSPH9 mutations demonstrated higher nasal
nitric oxide production (57nL/min Vs 15 nL/min, p <0.001), higher
FEV1 (-0.89 vs -2.37, p=0.018) and FVC (-1.00 vs -2.16, p=0.029) z-scores
than the rest of the cohort. Targeted multigene-panel NGS diagnosis is an
efficient single test for early diagnosis of PCD, providing insight to
disease genetic epidemiology in isolated populations and improved patient
stratification.