Advanced search
1 file | 2.92 MB

Genetic defects in TAPT1 disrupt ciliogenesis and cause a complex lethal osteochondrodysplasia

Author
Organization
Abstract
The evolutionarily conserved transmembrane anterior posterior transformation 1 protein, encoded by TAPT1, is involved in murine axial skeletal patterning, but its cellular function remains unknown. Our study demonstrates that TAPT1 mutations underlie a complex congenital syndrome, showing clinical overlap between lethal skeletal dysplasias and ciliopathies. This syndrome is characterized by fetal lethality, severe hypomineralization of the entire skeleton and intra-uterine fractures, and multiple congenital developmental anomalies affecting the brain, lungs, and kidneys. We establish that wild-type TAPT1 localizes to the centrosome and/or ciliary basal body, whereas defective TAPT1 mislocalizes to the cytoplasm and disrupts Golgi morphology and trafficking and normal primary cilium formation. Knockdown of tapt1b in zebrafish induces severe craniofacial cartilage malformations and delayed ossification, which is shown to be associated with aberrant differentiation of cranial neural crest cells.
Keywords
RECESSIVE OSTEOGENESIS IMPERFECTA, LINEAGE COMMITMENT, SKELETON, IDENTIFICATION, BONE FRAGILITY, MUTATION CAUSES, CRANIOFACIAL DEVELOPMENT, ZEBRAFISH, PRIMARY CILIA, I COLLAGEN

Downloads

  • (...).pdf
    • full text
    • |
    • UGent only
    • |
    • PDF
    • |
    • 2.92 MB

Citation

Please use this url to cite or link to this publication:

Chicago
Symoens, Sofie, Aileen M Barnes, Charlotte Gistelinck, Fransiska Malfait, Brecht Guillemyn, Wouter Steyaert, Delfien Syx, et al. 2015. “Genetic Defects in TAPT1 Disrupt Ciliogenesis and Cause a Complex Lethal Osteochondrodysplasia.” American Journal of Human Genetics 97 (4): 521–534.
APA
Symoens, Sofie, Barnes, A. M., Gistelinck, C., Malfait, F., Guillemyn, B., Steyaert, W., Syx, D., et al. (2015). Genetic defects in TAPT1 disrupt ciliogenesis and cause a complex lethal osteochondrodysplasia. AMERICAN JOURNAL OF HUMAN GENETICS, 97(4), 521–534.
Vancouver
1.
Symoens S, Barnes AM, Gistelinck C, Malfait F, Guillemyn B, Steyaert W, et al. Genetic defects in TAPT1 disrupt ciliogenesis and cause a complex lethal osteochondrodysplasia. AMERICAN JOURNAL OF HUMAN GENETICS. 2015;97(4):521–34.
MLA
Symoens, Sofie et al. “Genetic Defects in TAPT1 Disrupt Ciliogenesis and Cause a Complex Lethal Osteochondrodysplasia.” AMERICAN JOURNAL OF HUMAN GENETICS 97.4 (2015): 521–534. Print.
@article{7087628,
  abstract     = {The evolutionarily conserved transmembrane anterior posterior transformation 1 protein, encoded by TAPT1, is involved in murine axial skeletal patterning, but its cellular function remains unknown. Our study demonstrates that TAPT1 mutations underlie a complex congenital syndrome, showing clinical overlap between lethal skeletal dysplasias and ciliopathies. This syndrome is characterized by fetal lethality, severe hypomineralization of the entire skeleton and intra-uterine fractures, and multiple congenital developmental anomalies affecting the brain, lungs, and kidneys. We establish that wild-type TAPT1 localizes to the centrosome and/or ciliary basal body, whereas defective TAPT1 mislocalizes to the cytoplasm and disrupts Golgi morphology and trafficking and normal primary cilium formation. Knockdown of tapt1b in zebrafish induces severe craniofacial cartilage malformations and delayed ossification, which is shown to be associated with aberrant differentiation of cranial neural crest cells.},
  author       = {Symoens, Sofie and Barnes, Aileen M and Gistelinck, Charlotte and Malfait, Fransiska and Guillemyn, Brecht and Steyaert, Wouter and Syx, Delfien and D'hondt, Sanne and Biervliet, Martine and De Backer, Julie and Witten, Paul and Leikin, Sergey and Makareeva, Elena and Gillessen-Kaesbach, Gabriele and Huysseune, Ann and Vleminckx, Kris and Willaert, Andy and De Paepe, Anne and Marini, Joan C and Coucke, Paul},
  issn         = {0002-9297},
  journal      = {AMERICAN JOURNAL OF HUMAN GENETICS},
  keywords     = {RECESSIVE OSTEOGENESIS IMPERFECTA,LINEAGE COMMITMENT,SKELETON,IDENTIFICATION,BONE FRAGILITY,MUTATION CAUSES,CRANIOFACIAL DEVELOPMENT,ZEBRAFISH,PRIMARY CILIA,I COLLAGEN},
  language     = {eng},
  number       = {4},
  pages        = {521--534},
  title        = {Genetic defects in TAPT1 disrupt ciliogenesis and cause a complex lethal osteochondrodysplasia},
  url          = {http://dx.doi.org/10.1016/j.ajhg.2015.08.009},
  volume       = {97},
  year         = {2015},
}

Altmetric
View in Altmetric
Web of Science
Times cited: