Wallmeier, Julia, Frank, Diana, Shoemark, Amelia, Noethe-Menchen, Tabea, Cindric, Sandra, Olbrich, Heike, Loges, Niki T., Aprea, Isabella, Dougherty, Gerard W., Pennekamp, Petra, Kaiser, Thomas ORCID: 0000-0002-6699-0014, Mitchison, Hannah M., Hogg, Claire, Carr, Siobhan B., Zariwala, Maimoona A., Ferkol, Thomas, Leigh, Margaret W., Davis, Stephanie D., Atkinson, Jeffrey, Dutcher, Susan K., Knowles, Michael R., Thiele, Holger, Altmueller, Janine, Krenz, Henrike, Woeste, Marius, Brentrup, Angela, Ahrens, Frank, Vogelberg, Christian, Morris-Rosendahl, Deborah J. and Omran, Heymut (2019). De Novo Mutations in FOXJ1 Result in a Motile Ciliopathy with Hydrocephalus and Randomization of Left/Right Body Asymmetry. Am. J. Hum. Genet., 105 (5). S. 1030 - 1040. CAMBRIDGE: CELL PRESS. ISSN 1537-6605

Full text not available from this repository.

Abstract

Hydrocephalus is one of the most prevalent form of developmental central nervous system (CNS) malformations. Cerebrospinal fluid (CSF) flow depends on both heartbeat and body movement. Furthermore, it has been shown that CSF flow within and across brain ventricles depends on cilia motility of the ependymal cells lining the brain ventricles, which play a crucial role to maintain patency of the narrow sites of CSF passage during brain formation in mice. Using whole-exome and whole-genome sequencing, we identified an autosomal-dominant cause of a distinct motile ciliopathy related to defective ciliogenesis of the ependymal cilia in six individuals. Heterozygous de novo mutations in FOXJ1, which encodes a well-known member of the forkhead transcription factors important for ciliogenesis of motile cilia, cause a motile ciliopathy that is characterized by hydrocephalus internus, chronic destructive airway disease, and randomization of left/right body asymmetry. Mutant respiratory epithelial cells are unable to generate a fluid flow and exhibit a reduced number of cilia per cell, as documented by high-speed video microscopy (HVMA), transmission electron microscopy (TEM), and immunofluorescence analysis (IF). TEM and IF demonstrate mislocalized basal bodies. In line with this finding, the focal adhesion protein PTK2 displays aberrant localization in the cytoplasm of the mutant respiratory epithelial cells.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Wallmeier, JuliaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Frank, DianaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Shoemark, AmeliaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Noethe-Menchen, TabeaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cindric, SandraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Olbrich, HeikeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Loges, Niki T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Aprea, IsabellaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dougherty, Gerard W.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pennekamp, PetraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kaiser, ThomasUNSPECIFIEDorcid.org/0000-0002-6699-0014UNSPECIFIED
Mitchison, Hannah M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hogg, ClaireUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Carr, Siobhan B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zariwala, Maimoona A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ferkol, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Leigh, Margaret W.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Davis, Stephanie D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Atkinson, JeffreyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dutcher, Susan K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Knowles, Michael R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Thiele, HolgerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Altmueller, JanineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Krenz, HenrikeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Woeste, MariusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brentrup, AngelaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ahrens, FrankUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vogelberg, ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Morris-Rosendahl, Deborah J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Omran, HeymutUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-128025
DOI: 10.1016/j.ajhg.2019.09.022
Journal or Publication Title: Am. J. Hum. Genet.
Volume: 105
Number: 5
Page Range: S. 1030 - 1040
Date: 2019
Publisher: CELL PRESS
Place of Publication: CAMBRIDGE
ISSN: 1537-6605
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
PRIMARY CILIARY DYSKINESIA; CONGENITAL HEART-DISEASE; GENE-EXPRESSION; TRANSCRIPTION FACTORS; DEFECTS; CILIOGENESIS; DIAGNOSIS; CCDC39Multiple languages
Genetics & HeredityMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/12802

Downloads

Downloads per month over past year

Altmetric

Export

Actions (login required)

View Item View Item