title: Premature chromosome condensation in humans associated with microcephaly and mental retardation: a novel autosomal recessive condition.
abstract: We report a novel autosomal recessive disorder characterized by premature chromosome condensation in the early G2 phase. It was observed in two siblings, from consanguineous parents, affected with microcephaly, growth retardation, and severe mental retardation. Chromosome analysis showed a high frequency of prophase-like cells (>10%) in lymphocytes, fibroblasts, and lymphoblast cell lines with an otherwise normal karyotype. (3)H-thymidine-pulse labeling and autoradiography showed that, 2 h after the pulse, 28%-35% of the prophases were labeled, compared with 9%-11% in healthy control subjects, indicating that the phenomenon is due to premature chromosome condensation. Flow cytometry studies demonstrate that the entire cell cycle is not prolonged, compared with that in healthy control subjects, and compartment sizes did not differ from those in healthy control subjects. No increased reaction of the cells to X-irradiation or treatments with the clastogens bleomycin and mitomycin C was observed, in contrast to results in the cell-cycle mutants ataxia telangiectasia and Fanconi anemia. The rates of sister chromatid exchanges and the mitotic nondisjunction rates were inconspicuous. Premature entry of cells into mitosis suggests that a gene involved in cell-cycle regulation is mutated in these siblings.
authors.affiliation: Institute of Human Genetics, Charité, Campus Virchow, Humboldt University-Berlin, Augustenburger Platz 1, D-13353 Berlin, Germany. heidemarie.neitzel@charite.de
authors.forename: Heidemarie
authors.initials: H
authors.lastname: Neitzel
authors.forename: Luitgard M
authors.initials: LM
authors.lastname: Neumann
authors.forename: Detlev
authors.initials: D
authors.lastname: Schindler
authors.forename: Andreas
authors.initials: A
authors.lastname: Wirges
authors.forename: Holger
authors.initials: H
authors.lastname: Tönnies
authors.forename: Marc
authors.initials: M
authors.lastname: Trimborn
authors.forename: Alice
authors.initials: A
authors.lastname: Krebsova
authors.forename: Reyk
authors.initials: R
authors.lastname: Richter
authors.forename: Karl
authors.initials: K
authors.lastname: Sperling
mesh_terms: D002453:Cell Cycle; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D002843:Chromatin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D020090:Chromosome Segregation / Q000235:genetics; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics; D003241:Consanguinity; D005260:Female; D005347:Fibroblasts / Q000473:pathology; D005434:Flow Cytometry; D005808:Genes, Recessive / Q000235:genetics*; D006130:Growth Disorders / Q000150:complications / Q000235:genetics / Q000473:pathology; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008607:Intellectual Disability / Q000150:complications* / Q000235:genetics* / Q000473:pathology; D008214:Lymphocytes / Q000473:pathology; D008297:Male; D008831:Microcephaly / Q000150:complications / Q000235:genetics / Q000473:pathology; D008968:Molecular Conformation; D009630:Nondisjunction, Genetic; D012854:Sister Chromatid Exchange / Q000235:genetics; D013997:Time Factors
chemical_list: D002843:Chromatin