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|Abstract:||Primary ciliary dyskinesia (PCD) is a genetically heterogeneous autosomal recessive disorder characterized by recurrent infections of the respiratory tract associated with abnormal function of motile cilia. Approximately half of PCD patients also have alterations in the left-right organization of internal organ positioning including situs inversus and situs ambiguous (Kartagener’s Syndrome, KS). Here we identify an uncharacterized coiled-coil domain containing protein (CCDC40) essential for correct left-right patterning in mouse, zebrafish and humans. Ccdc40 is expressed in tissues that contain motile cilia and mutation of Ccdc40 results in cilia with reduced ranges of motility. Importantly, we demonstrate that CCDC40 deficiency causes a novel PCD variant characterized by misplacement of central pair microtubules and defective axonemal assembly of inner dynein arms (IDAs) and dynein regulator complexes (DRCs). CCDC40 localizes to motile cilia and the apical cytoplasm and is responsible for axonemal recruitment of CCDC39, which is also mutated in a similar PCD variant.|
|Electronic Publication Date:||5-Dec-2010|
|Citation:||Becker-Heck, Anita, Zohn, Irene E., Okabe, Noriko, Pollock, Andrew, Lenhart, Kari Baker, Sullivan-Brown, Jessica, McSheene, Jason, Loges, Niki T., Olbrich, Heike, Haeffner, Karsten, Fliegauf, Manfred, Horvath, Judith, Reinhardt, Richard, Nielsen, Kim G., Marthin, June K., Baktai, Gyorgy, Anderson, Kathryn V., Geisler, Robert, Niswander, Lee, Omran, Heymut, Burdine, Rebecca D. (2011). The coiled-coil domain containing protein CCDC40 is essential for motile cilia function and left-right axis formation. Nature Genetics, 43 (1), 79 - 84. doi:10.1038/ng.727|
|Pages:||79 - 84|
|Type of Material:||Journal Article|
|Journal/Proceeding Title:||Nature Genetics|
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