Chromosomal instability syndrome of total premature chromatid separation with mosaic variegated aneuploidy is defective in mitotic-spindle checkpoint

Am J Hum Genet. 2000 Aug;67(2):483-6. doi: 10.1086/303022. Epub 2000 Jun 30.


Skin fibroblast cells from two unrelated male infants with a chromosome-instability disorder were analyzed for their response to colcemid-induced mitotic-spindle checkpoint. The infants both had severe growth and developmental retardation, microcephaly, and Dandy-Walker anomaly; developed Wilms tumor; and one died at age 5 mo, the other at age 3 years. Their metaphases had total premature chromatid separation (total PCS) and mosaic variegated aneuploidy. Mitotic-index analysis of their cells showed the absence of mitotic block after the treatment with colcemid, a mitotic-spindle inhibitor. Bromodeoxyuridine-incorporation measurement and microscopic analysis indicated that cells treated with colcemid entered G1 and S phases without sister-chromatid segregation and cytokinesis. Preparations of short-term colcemid-treated cells contained those cells with chromosomes in total PCS and all or clusters of them encapsulated by nuclear membranes. Cell-cycle studies demonstrated the accumulation of cells with a DNA content of 8C. These findings indicate that the infants' cells were insensitive to the colcemid-induced mitotic-spindle checkpoint.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abnormalities, Multiple / genetics*
  • Abnormalities, Multiple / pathology
  • Aneuploidy*
  • Cells, Cultured
  • Child, Preschool
  • Chromatids / drug effects
  • Chromatids / genetics
  • Chromatids / pathology*
  • Chromosome Fragility / genetics*
  • Chromosome Segregation / drug effects
  • Chromosome Segregation / genetics*
  • DNA / biosynthesis
  • Demecolcine / pharmacology
  • Fibroblasts
  • Flow Cytometry
  • Growth Disorders / genetics
  • Growth Disorders / pathology
  • Humans
  • Infant
  • Male
  • Metaphase / drug effects
  • Mitotic Index / drug effects
  • Mosaicism / genetics*
  • Mosaicism / pathology
  • Nuclear Envelope / drug effects
  • Skin / pathology
  • Spindle Apparatus / drug effects
  • Spindle Apparatus / pathology*
  • Syndrome
  • Wilms Tumor / genetics
  • Wilms Tumor / pathology


  • DNA
  • Demecolcine