Summary
We present clinical and biochemical data from three patients with severe Cockayne syndrome (CS) of very early onset. Unlike in classic CS, signs became evident in the first weeks of life and led to unusually early death. Fibroblasts from two of the patients showed a complete defect of the repair of UV-induced thymine dimer lesions. They were unable to remove thymine dimer lesions from their DNA, had a severe reduction of the RNA synthesis rates after UV irradiation, and showed no reactivation of an UV-inactivated indicator gene and no DNA recondensation after UV irradiation. DNA repair investigated in these two fibroblast cell strains resembled that of xeroderma pigmentosum cells of complementation group A. In contrast, fibroblasts from the third patient showed the same in vitro repair characteristics as classic CS cells.
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References
Andrews AD, Barrett SF, Yoder FW, Robbins JH (1978) Cockayne's syndrome fibroblasts have increased sensitivity to ultraviolet light but normal rates of unscheduled DNA synthesis. J Invest Dermatol 70:237–239
Chu EHY, Schmickel RD, Wade MH, Chang CC, Trosko JE (1975) Ultraviolet light intensity and defect in DNA repair in fibroblasts derived from two patients with Cockayne syndrome. Am J Hum Genet 27:26a
Cleaver JE (1982) Normal reconstruction of DNA supercoiling and chromatin structure in Cockayne syndrome cells during repair of damage from ultraviolet light. Am J Hum Genet 34:566–575
Cook PR, Brazell IA (1976) Detection and repair of single strand breaks in nuclear DNA. Nature 263:679–682
Fujiwara Y, Goto K, Kano Y (1982) Ultraviolet hypersensitivity of Cockayne's syndrome fibroblasts. Exp Cell Res 139:207–215
Gorman CM, Moffat LF, Howard BH (1982) Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells. Mol Cell Biol 2:1044–1051
Grunnet ML, Zimmerman AW, Lewis RA (1983) Ultrastructure and electrodiagnosis of peripheral neuropathy in Cockayne's syndrome. Neurology 33:1606–1609
Houston CS, Zaleski WA, Rozdilsky B (1982) Identical twins and brother with Cockayne syndrome. Am J Med Genet 13:211–223
Kantor GJ, Setlow RB (1981) Rate and extent of DNA repair in nondividing human diploid fibroblasts. Cancer Res 41:819–825
Klocker H, Auer B, Burtscher HJ, Hofmann J, Hirsch-Kauffmann M, Schweiger M (1982) A sensitive radioimmunoassay for thymine dimers. 186:475–477
Klocker H, Auer B, Burtscher HJ, Hirsch-Kaufmann M, Schweiger M (1984) A synthetic hapten for induction of thymine-dimer-specific antibodies. Eur J Biochem 142:313–316
Klocker H, Schneider R, Burtscher HJ, Auer B, Hirsch-Kauffmann M, Schweiger M (1985) Transient expression of a plasmid gene, a tool to study DNA repair in human cells: defect of DNA repair in Cockayne syndrome; one thymine cyclobutane dimer is sufficient to block transcription. Eur J Cell Biol 39:346–351
Landing BH, Sugarman G, Dixon LG (1983) Eccrine sweat gland anatomy in Cockayne syndrome: a possible diagnostic aid. Pediatr Pathol 1:349–353
Lehmann AR (1982) Three complementation groups in Cockayne syndrome. Mutat Res 106:347–356
Lehmann AR, Mayne L (1981) The response of Cockayne syndrome cells to UV-irradiation. In: Seeberg E, Kleppe K (eds) Chromosome damage and repair. Plenum Press, New York London, pp 367–371
Lehmann AR, Kirk-Bell S, Mayne L (1979) Abnormal kinetics of DNA synthesis in ultraviolet light-irradiated cells from patients with Cockayne's syndrome. Cancer Res 39:4237–4241
Levinson ED, Zimmerman AW, Grunnet ML, Lewis RA, Spackman RJ (1982) Cockayne syndrome. J Comput Assist Tomogr 6:1172–1174
Lytle CD, Tarone RE, Barrett SF, Wirtschafter JD, Dupuy J-M, Robbins JH (1983) Host cell reactivation by fibroblasts from patients with pigmentary degeneration of the retina. Photochem Photobiol 37:503–508
Marshall RR, Arlett CF, Harcourt SA, Broughton BA (1980) Increased sensitivity of cell strains from Cockayne's syndrome to sister-chromatid-exchange induction and cell killing by UV light. Mutat Res 69:107–112
Mayne LV, Lehmann AR (1982) Failure of RNA synthesis to recover after UV irradiation: an early defect in cells from individuals with Cockayne's syndrome and xeroderma pigmentosum. Cancer Res 42:1473–1478
Mayne LV, Lehmann AR, Waters R (1982) Excision repair in Cockayne syndrome. Mutat Res 106:179–189
Moshell AN, Ganges MB, Lutzner MA, Coon HG, Barrett SF, Dupuy J-M, Robbins JH (1983) A new patient with both xeroderma pigmentosum and Cockayne syndrome establishes the new xeroderma pigmentosum complementation group H. In: Cellular responses to DNA damage. Liss, New York, pp 209–213
Moyer DB, Marquis P, Shertzer ME, Burton BK (1982) Brief clinical report: Cockayne syndrome with early onset of manifestations. Am J Med Genet 13:225–230
Nishio H, Kodama S, Matsuo T, Ichihashi M, Ito H, Fujiwara Y (1988) Cockayne syndrome: magnetic resonance images of the brain in a severe form with early onset. J Inherited Metab Dis 11:88–102
Protic-Sabljic M, Kraemer KH (1985) One pyrimidine dimer inactivates expression of a transfected gene in xeroderma pigmentosum cells. Proc Natl Acad Sci USA 82:6622–6626
Robbins JH, Kraemer KH, Lutzner MA, Festoff BW, Coon HG (1974) Xeroderma pigmentosum: an inherited disease with sun sensitivity, multiple cutaneous neoplasms and abnormal DNA repair. Ann Intern Med 80:221–248
Ryan DKG, Rainbow AJ (1986) Comparative studies of host cell reactivation, cellular capacity and enhanced reactivation of herpes simplex virus in normal, xeroderma pigmentosum and Cockayne syndrome fibroblasts. Mutat Res 166:99–111
Schmickel RD, Chu EHY, Trosko JE, Chang CC (1977) Cockayne syndrome: a cellular sensitivity to ultraviolet light. Pediatrics 60: 135–139
Schwaiger H, Hirsch-Kauffmann M, Schweiger M (1986) DNA repair in human cells: in Cockayne syndrome cells rejoining of DNA strands is impaired. Eur J Cell Biol 41:352–355
Silengo MC, Franceschini P, Bianco R, Biagioli M, Pastorin L, Vista N, Baldassar A, Benso L (1986) Distinctive skeletal dysplasia in Cockayne syndrome. Pediatr Radiol 16:264–266
Smits MG, Gabreels FJM, Renier WO, Joosten EMG, Gabreels-Festen AWM, Ter Laak HJ, Pinckers AJL, Hombergen GCJ, Notermans SLH, Thyssen HOM (1982) Peripheral and central myelinopathy in Cockayne's syndrome. Report of 3 siblings. Neuropediatrics 13:161–167
Tanaka K, Kawai K, Kumahara Y, Ikenaga M, Okada Y (1981) Genetic complementation groups in Cockayne syndrome. Somatic Cell Genet 7:445–455
Wade MH, Chu EHY (1979) Effects of DNA damaging agents on cultured fibroblasts derived from patients with Cockayne syndrome. Mutat Res 59:49–60
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Jacken, J., Klocker, H., Schwaiger, H. et al. Clinical and biochemical studies in three patients with severe early infantile Cockayne syndrome. Hum Genet 83, 339–346 (1989). https://doi.org/10.1007/BF00291378
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DOI: https://doi.org/10.1007/BF00291378