Details

Autor(en) / Beteiligte

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

Titel

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

Ist Teil von

• American journal of human genetics, 2015-10, Vol.97 (4), p.521-534

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2015

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.