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Chromosomal breakage, endomitosis, endoreduplication, and hypersensitivity toward radiomimetric and alkylating agents: A possible new autosomal recessive mutation in a girl with craniosynostosis and microcephaly

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Abstract

A high frequency of spontaneous chromosomal breakage, endomitosis, endoreduplication and hypersensitivity toward both the alkylating agent Trenimon and the radiomimetric drug bleomycin was observed in phytohemagglutinin-stimulated peripheral lymphocytes from a girl with craniosynostosis, microcephaly, ptosis, bird-like facies, and moderate mental retardation. We also observed abnormal chromosomal spiralization and some aspects of abnormal cellular division. Several fruitless attempts were made to establish a cell line. The parents were consanguineous, supporting the existence of a new, rare, autosomal, recessive condition in man. The mutation might involve a gene involved in DNA repair and/or regulation of the mitotic cycle.

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References

  • Barnes DE, Tomlinson AE, Lehmann AR, Webster ADB, Lindahl T (1992) Mutations in the DNA ligase I gene of an individual with immunodeficiencies and cellular hypersensitivity to DNAdamaging agents. Cell 69:495–503

    Google Scholar 

  • Bloom D (1954) Congenital teleangiectagic erythema resembling lupus erythematosis in dwarfs: probably a syndrome entity. Am J Dis Child 88:754–758

    Google Scholar 

  • Bloom GE, Warner S, Gerald PS, Diamond LK (1966) Chromosome abnormalities in constitutional aplastic anemia. N Engl J Med 274:8–14

    Google Scholar 

  • Caspersson T, Zech L, Johannson C, Modest EJ (1970) Identification of human chromosomes by DNA-binding fluorescent agents. Chromosoma 30:215–227

    Google Scholar 

  • Chaganti RSK, Schonberg S, German J (1974) A manyfold increase in sister chromatid exchanges in Bloom's syndrome. Proc Natl Acad Sci USA 71:4508–4512

    Google Scholar 

  • Chan JYH, Becker FF, German J, Ray JH (1987) Altered DNA ligase I activity in Bloom's syndrome cells. Nature 325:357–359

    Google Scholar 

  • Couturier J, Dutrillaux B, Lejeune J (1973) Etude des fluorescences spécifiques des bandes R et des bandes Q des chromosomes humains. CR Acad Sci Ser D 276:339–342

    Google Scholar 

  • Dunphy WG, Newport JW (1988) Unraveling of mitotic control mechanisms. Cell 55:925–928

    Google Scholar 

  • Fanconi G (1966) Familial constitutional panmyelocytopathy, Fanconi's anemia (F.A.) Clinical aspects. Semin Hematol 4:233–240

    Google Scholar 

  • Geitler L (1939) Die Entstehung der polyploiden Somakerne der Heteropteren durch Chromosomenteilung ohne Kernteilung. Chromosoma 1:1–22

    Google Scholar 

  • German J, Archibald R, Bloom D (1965) Chromosomal breakage in a rare and probably genetically determined syndrome of man. Science 148:506–507

    Google Scholar 

  • Hecht F, Koler RD, Rigas DA, Dahnke GS, Case MP, Tidale V, Miller RW (1966) Leukemia and lymphocytes in ataxia-telangiectasia. Lancet II:1193

    Google Scholar 

  • Hickson ID, Harris AL (1988) Mammalian DNA repair — use of mutants hypersensitive to cytotoxic agents. Trends Genet 4:101–106

    Google Scholar 

  • Ishizaki K, Yagi T, Inoue M, Nikaido O, Takebe H (1981) DNA repair in Bloom's syndrome fibroblasts after UV irradiation or treatment with mitomycin C. Mutat Res 80:213–219

    Google Scholar 

  • Kubbies M, Schindler D, Hoehn H, Rabinovitch PS (1985) Cell cycle kinetics by BrdU/-Hoechst flow cytometry. Cell Tissue Kinet 18:551–552

    Google Scholar 

  • Kurihara T, Inoue M, Tatsumi K (1987) Hypersensitivity of Bloom's syndrome fibroblasts to N-ethyl-N-nitrosourea. Mutat Res 184:147–151

    Google Scholar 

  • Levan A, Hauschka TS (1953) Endomitotic reduplication mechanisms in ascites tumors of the mouse. J Natl Cancer Inst 14:1–43

    Google Scholar 

  • Murray AW (1989) The cell cycle as a cdc2 cycle. Nature 342:14–15

    Google Scholar 

  • Perry P, Wolff S (1974) New Giemsa method for the differential staining of sister chromatids. Nature 251:156–158

    Google Scholar 

  • Pippard EC, Hall AJ, Barker DJP, Bridges BA (1988) Cancer in homozygotes and heterozygotes of ataxia-telangiectasia and xeroderma pigmentosum in Britain. Cancer Res 48:2929–2932

    Google Scholar 

  • Sarto GE, Stubblefield PA, Therman E (1982) Endomitosis in human trophoblast. Hum Genet 62:228–232

    Google Scholar 

  • Sasaki MS (1975) Is Fanconi's anemia defective in a process essential to the repair of DNA cross links? Nature 257:501–503

    Google Scholar 

  • Sasaki MS, Tonomura A (1973) A high susceptibility of Fanconi's anemia to chromosome breakage by DNA cross-linking agents. Cancer Res 33:1829–1836

    Google Scholar 

  • Schroeder TM, Anschutz F, Knopp A (1964) Spontane Chromosomenaberrationen bei familiärer Panmyelopathie. Humangenetik 1:194–196

    Google Scholar 

  • Strathdee CA, Gavish H, Shannon WR, Buchwald M (1992) Cloning of cDNAs for Fanconi's anemia by functional complementation. Nature 356:763–767

    Google Scholar 

  • Swift M, Reitnauer PJ, Morrell D, Chase CL (1987) Breast and other cancers in families with ataxia-telangiectasia. N Engl J Med 316:1289–1294

    Google Scholar 

  • Taylor AMR, Harnden DG, Arlett CF, Harcourt SA, Lehmann AR, Stevens S, Bridges BA (1975) Ataxia-telangiectasia: a human mutation with abnormal radiation sensitivity. Nature 258:427–429

    Google Scholar 

  • Taylor AMR, Rosney CM, Campbell JE (1979) Unusual sensitivity of ataxia-telangiectasia cells to bleomycin. Cancer Res 39:1046–1050

    Google Scholar 

  • Therman E, Sarto GE, Stubblefield PA (1983) Endomitosis: a reappraisal. Hum Genet 63:13–18

    Google Scholar 

  • Tommerup N (1982) Specific staining of 9 h in human somatic interphase cells by D 287/170. Hum Genet 62:301–304

    Google Scholar 

  • Weemaes CMR, Hustinx TWJ, Scheres JMJC, Munster PJJ v, Bakkeren JAJ, Taalman DFM (1981) A new chromosomal instability disorder: the Nijmegen breakage syndrome. Acta Paediatr Scand 70:555–564

    Google Scholar 

  • Wegner R-D (1991) Chromosomal instability syndromes in man. In: Obe G (ed) Advances in mutagenesis research, vol 3. Springer, Berlin Heidelberg New York, pp 81–130

    Google Scholar 

  • Wegner R-D, Metzger M, Hanefeld F, Jaspers NGJ, Baan C, Magdorf K, Kunze J, Sperling K (1988) A new chromosomal instability disorder confirmed by complementation studies. Clin Genet 33:20–32

    Google Scholar 

  • Willis AE, Lindahl T (1987) DNA ligase I deficiency in Bloom's syndrome. Nature 325:355–357

    Google Scholar 

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Tommerup, N., Mortensen, E., Nielsen, M.H. et al. Chromosomal breakage, endomitosis, endoreduplication, and hypersensitivity toward radiomimetric and alkylating agents: A possible new autosomal recessive mutation in a girl with craniosynostosis and microcephaly. Hum Genet 92, 339–346 (1993). https://doi.org/10.1007/BF01247331

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  • DOI: https://doi.org/10.1007/BF01247331

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