Genetic Characterization of Primary Ciliary Dyskinesia in a Consanguineous Population: Insights From the Largest Middle Eastern Cohort.

Background: Primary Ciliary Dyskinesia (PCD) is a Mendelian disorder most commonly inherited in an autosomal recessive pattern. It impairs the mucociliary clearance in the respiratory system. As genetic variants linked to this disorder continue to be identified, genetic testing becomes more accessible. This study aimed to characterize genetic variants associated with PCD in a consanguineous population.

Methods: Medical records of 327 affected individuals from 242 families, all strongly suspected of having PCD, were reviewed. All patients exhibited at least two of the four main clinical symptoms of PCD: unexplained neonatal respiratory distress in term infants, year-round daily cough since infancy, year-round nasal congestion since infancy, or organ laterality defects.

Results: Out of the cohort, 130 affected individuals from 117 families underwent genetic testing, which included targeted Sanger sequencing, exome sequencing, or panel sequencing. The genetic diagnostic rate was 33%, with 43 of these 130 patients from 24 families receiving a molecular diagnosis. Electron microscopy (EM) revealed ciliary ultrastructural defects in 13 of the 43 patients, which correlated with their genetic variants.

Conclusions: This represents the largest cohort of PCD patients from the Middle East. The findings highlight the genetic diversity of PCD and underscore the importance of genetic testing for diagnosis. We report novel variants and contribute to the growing understanding of the genetic causes of PCD. Early genetic diagnosis can significantly influence timely management, helping to prevent lung damage and other complications associated with this challenging disease.

Clinical trial number: Not applicable.