Primary Ciliary Dyskinesia Diagnostic Challenges: Understanding the Clinical Phenotype of the Puerto Rican RSPH4A Founder Mutation

Abstract

Primary ciliary dyskinesia (PCD) is a rare, heterogeneous ciliopathy resulting in chronic oto-sino-pulmonary disease, bronchiectasis, newborn respiratory distress, and laterality defects. PCD diagnosis can be achieved by following diagnostic algorithms that include electron microscopy, genetics, and ancillary testing. Genetic mutations in more than 45 genes, including <i>RSPH4A</i>, can lead to PCD. <i>RSPH4A</i> mutations located on chromosome six, affect radial spokes and results in central complex apparatus abnormalities. The <i>RSPH4A</i> [c.921 + 3_6delAAGT] founder mutation was described as one cause of PCD without laterality defects in Puerto Rico. Additionally, there are further diagnostic challenges present in the Puerto Rican population to diagnose PCD. We describe the demographics, clinical features, and <i>RSPH4A</i> genetic variants in 13 patients with clinical PCD affecting 11 Puerto Ricans from unrelated families.