Identifying Novel Genetic Causes of Primary Ciliary Dyskinesia

Primary ciliary dyskinesia (PCD) is a disease that affects the function of respiratory cilia that helps protect against airway infections. Diagnosis is difficult with current methods but genetic testing may expedite the process since PCD is hereditary, however the etiology of 30% of cases remains unknown. To identify more causes of PCD, whole exome sequencing was performed on patients identifying Spindly (spdl1) as a candidate. Analysis using zebrafish indicate spdl1 is expressed in motile ciliated tissues. Spdl1 deficiency results in embryos with ventral curvatures indicating cilia dysfunction. The defects can be rescued with 100pg of WT RNA but not RNA containing one of the mutations identified. Cilia orientation and range of motion was unaffected but motile cilia length was significantly increased in mutant neural tube floorplate (p