Open AccessDisturbed chromosome segregation and multipolar spindle formation in a patient with CHAMP 1 mutation
Author(s) -
Okamoto Nobuhiko,
Tsuchiya Yuki,
Kuki Ichiro,
Yamamoto Toshiyuki,
Saitsu Hirotomo,
Kitagawa Daiju,
Matsumoto Naomichi
Publication year - 2017
Publication title -
molecular genetics and genomic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.765
H-Index - 29
ISSN - 2324-9269
DOI - 10.1002/mgg3.303
Subject(s) - cytokinesis , centrosome , biology , genetics , mitosis , phenotype , frameshift mutation , mutation , midbody , multipolar spindles , microbiology and biotechnology , spindle apparatus , spindle checkpoint , exome sequencing , plk1 , chromosome segregation , chromosome , kinetochore , gene , cell division , cell cycle , cell
Background Patients with intellectual disability ( ID ) typically exhibit significant defects in both intelligence and adaptive behavior. Aberration of several genes involved in proper progression of mitosis has been reported to underlie ID . Here, we report a new patient with a novel mutation of CHAMP 1 . Methods Whole exome sequencing ( WES ) analysis was performed. We isolated lymphoblast cells from the CHAMP 1 patient and observed chromosome segregation. Results We identified a de novo frameshift mutation in CHAMP 1 . We find that these cells exhibit an increase in centrosome number and resulting multipolar spindle formation. The phenotypes observed in the patient's lymphoblastoid cells were presumably because of cytokinesis failure. We also confirm the identical phenotypes in human culture cells depleted of CHAMP 1. Conclusion CHAMP 1 encodes a protein regulating kinetochore–microtubule attachment and chromosome segregation. These data strongly support that CHAMP 1 mutations cause ID , and suggest that CHAMP 1 is critical for progression of cytokinesis and maintenance of centrosome number.