title: Chromosomal instability syndrome of total premature chromatid separation with mosaic variegated aneuploidy is defective in mitotic-spindle checkpoint.
abstract: 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.
authors.affiliation: Department of Radiation Biology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Matsuura
authors.forename: E
authors.initials: E
authors.lastname: Ito
authors.forename: H
authors.initials: H
authors.lastname: Tauchi
authors.forename: K
authors.initials: K
authors.lastname: Komatsu
authors.forename: T
authors.initials: T
authors.lastname: Ikeuchi
authors.forename: T
authors.initials: T
authors.lastname: Kajii
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics* / Q000473:pathology; D000782:Aneuploidy; D002478:Cells, Cultured; D002675:Child, Preschool; D002842:Chromatids / Q000187:drug effects / Q000235:genetics / Q000473:pathology*; D002873:Chromosome Fragility / Q000235:genetics*; D020090:Chromosome Segregation / Q000187:drug effects / Q000235:genetics*; D004247:DNA / Q000096:biosynthesis; D003703:Demecolcine / Q000494:pharmacology; D005347:Fibroblasts; D005434:Flow Cytometry; D006130:Growth Disorders / Q000235:genetics / Q000473:pathology; D006801:Humans; D007223:Infant; D008297:Male; D008677:Metaphase / Q000187:drug effects; D008940:Mitotic Index / Q000187:drug effects; D009030:Mosaicism / Q000235:genetics* / Q000473:pathology; D009685:Nuclear Envelope / Q000187:drug effects; D012867:Skin / Q000473:pathology; D008941:Spindle Apparatus / Q000187:drug effects / Q000473:pathology*; D013577:Syndrome; D009396:Wilms Tumor / Q000235:genetics / Q000473:pathology
chemical_list: D004247:DNA; D003703:Demecolcine