Genetic Defects in TAPT1 Disrupt Ciliogenesis and Cause a Complex Lethal Osteochondrodysplasia

Sofie Symoens, Aileen M. Barnes, Charlotte Gistelinck, Fransiska Malfait, Brecht Guillemyn, Wouter Steyaert, Delfien Syx, Sanne D'Hondt, Martine Biervliet, Julie De Backer, Eckhard P. Witten, Sergey Leikin, Elena Makareeva, Gabriele Gillessen-Kaesbach, Ann Huysseune, Kris Vleminckx, Andy Willaert, Anne De Paepe, Joan C. Marini, Paul J. Coucke*

*Corresponding author for this work
19 Citations (Scopus)


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.

Original languageEnglish
JournalAmerican Journal of Human Genetics
Issue number4
Pages (from-to)521-534
Number of pages14
Publication statusPublished - 2015

Research Areas and Centers

  • Research Area: Medical Genetics


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