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

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

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)e0189324
JournalPLoS One
Volume12
Issue number12
DOIs
StatePublished - Jan 1 2017

Fingerprint

Kinetochores
kinetochores
Defects
Growth
Cell Division
Cells
cell division
Proteins
proteins
growth disorders
Growth Disorders
Genes
Centrioles
centrosomes
Centrosome
centrioles
Spindle Apparatus
human cell lines
genes
Zebrafish

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Hung, C. Y., Volkmar, B., Baker, J., Bauer, J. W., Gussoni, E., Hainzl, S., ... Bodamer, O. A. (2017). A defect in the inner kinetochore protein CENPT causes a new syndrome of severe growth failure. PLoS One, 12(12), e0189324. https://doi.org/10.1371/journal.pone.0189324

A defect in the inner kinetochore protein CENPT causes a new syndrome of severe growth failure. / Hung, Christina Y.; Volkmar, Barbara; Baker, James; Bauer, Johann W.; Gussoni, Emanuela; Hainzl, Stefan; Klausegger, Alfred; Lorenzo, Jose; Mihalek, Ivana; Rittinger, Olaf; Tekin, Mustafa; Dallman, Julia; Bodamer, Olaf A.

In: PLoS One, Vol. 12, No. 12, 01.01.2017, p. e0189324.

Research output: Contribution to journalArticle

Hung, CY, Volkmar, B, Baker, J, Bauer, JW, Gussoni, E, Hainzl, S, Klausegger, A, Lorenzo, J, Mihalek, I, Rittinger, O, Tekin, M, Dallman, J & Bodamer, OA 2017, 'A defect in the inner kinetochore protein CENPT causes a new syndrome of severe growth failure', PLoS One, vol. 12, no. 12, pp. e0189324. https://doi.org/10.1371/journal.pone.0189324
Hung, Christina Y. ; Volkmar, Barbara ; Baker, James ; Bauer, Johann W. ; Gussoni, Emanuela ; Hainzl, Stefan ; Klausegger, Alfred ; Lorenzo, Jose ; Mihalek, Ivana ; Rittinger, Olaf ; Tekin, Mustafa ; Dallman, Julia ; Bodamer, Olaf A. / A defect in the inner kinetochore protein CENPT causes a new syndrome of severe growth failure. In: PLoS One. 2017 ; Vol. 12, No. 12. pp. e0189324.
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