HYDINvariants cause primary ciliary dyskinesia in the Finnish population

Abstract

AbstractPrimary ciliary dyskinesia (PCD) is a rare genetic disorder characterized by chronic respiratory tract infections and in some cases laterality defects and infertility. The symptoms of PCD are caused by malfunction of motile cilia, hair-like organelles protruding out of the cell that are responsible for removal of mucus from the airways, organizing internal organ positioning during embryonic development and gamete transport. PCD is caused by mutations in genes coding for structural or assembly proteins of motile cilia. Thus far, mutations in over 50 genes have been identified and these variants explain around 70% of all known cases. Population specific genetics underlying PCD has been reported underlining the importance of characterizing gene variants in different populations for development of gene-based diagnostics and management. In this study, we identified disease causing genetic variants in the axonemal central pair component HYDIN. Three Finnish PCD patients carried homozygous loss-of-function variants and one patient had compound heterozygous variants within theHYDINgene. The functional effect of theHYDINvariants was confirmed by immunofluorescence and electron tomography, which demonstrated defects in the axonemal central pair complex. All patients had clinical PCD symptoms including chronic wet cough and recurrent airway infections due to almost static airway cilia. Our results are consistent with the previously identified important role of HYDIN in the axonemal central pair complex and improve specific diagnostics of PCD in different ethnical backgrounds.