Naslov
A defect in the inner kinetochore protein CENPT causes a new syndrome of severe growth failure

Autori
Hung, Christina Y. ; Volkmar, Barbara ; Baker, James D. ; Bauer, Johann W. ; Gussoni, Emanuela ; Hainzl, Stefan ; Klausegger, Alfred ; Lorenzo, Jose ; Mihalek, Ivana ; Rittinger, Olaf ; Tekin, Mustafa ; Dallman, Julia E. ; Bodamer, Olaf A.

Izvornik
PLOS ONE (1932-6203) 12 (2017), 12; 0189324, 17

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
CENPT ; syndrome of severe growth failure

Sažetak
Primordial growth failure has been linked to defects in the biology of cell division and replication. The complex processes involved in microtubule spindle formation, organization and function have emerged as a dominant patho-mechanism in these conditions. The majority of reported disease genes encode for centrosome and centriole proteins, leaving kinetochore proteins by which the spindle apparatus interacts with the chromosomes largely unaccounted for. We report a novel disease gene encoding the constitutive inner kinetochore member CENPT, which is involved in kinetochore targeting and assembly, resulting in severe growth failure in two siblings of a consanguineous family. We herein present studies on the molecular and cellular mechanisms that explain how genetic mutations in this gene lead to primordial growth failure. In both, affected human cell lines and a zebrafish knock-down model of Cenpt, we observed aberrations in cell division with abnormal accumulation of micronuclei and of nuclei with increased DNA content arising from incomplete and/or irregular chromosomal segregation. Our studies underscore the critical importance of kinetochore function for overall body growth and provide new insight into the cellular mechanisms implicated in the spectrum of these severe growth disorders.

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Biotehnologija u biomedicini (prirodno područje, biomedicina i zdravstvo, biotehničko područje)

POVEZANOST RADA