A1 Refereed original research article in a scientific journal
CFAP300 mutation causing primary ciliary dyskinesia in Finland
Authors: Schultz Rüdiger, Elenius Varpu, Fassad Mahmoud R, Freke Grace, Rogers Andrew, Shoemark Amelia, Koistinen Tiina, Mohamed Mai A, Lim Jaqueline SY, Mitchison Hannah M, Sironen Anu I
Publisher: Frontiers Media SA
Publication year: 2022
Journal: Frontiers in Genetics
Journal name in source: FRONTIERS IN GENETICS
Journal acronym: FRONT GENET
Article number: 985227
Volume: 13
Number of pages: 11
eISSN: 1664-8021
DOI: https://doi.org/10.3389/fgene.2022.985227
Web address : https://doi.org/10.3389/fgene.2022.985227
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/176905072
Primary ciliary dyskinesia (PCD) is a rare genetic condition 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 and organizing internal organ positioning during embryonic development. PCD is caused by mutations in genes coding for structural or assembly proteins in 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, thus highlighting the importance of characterizing gene variants in different populations for development of gene-based diagnostics. In this study, we identified a recurrent loss-of-function mutation c.198_200delinsCC in CFAP300 causing lack of the protein product. PCD patients homozygous for the identified CFAP300 mutation have immotile airway epithelial cilia associated with missing dynein arms in their ciliary axonemes. Furthermore, using super resolution microscopy we demonstrate that CFAP300 is transported along cilia in normal human airway epithelial cells suggesting a role for CFAP300 in dynein complex transport in addition to preassembly in the cytoplasm. Our results highlight the importance of CFAP300 in dynein arm assembly and improve diagnostics of PCD in Finland.
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