Skip to content

Research at St Andrews

Dyskeratosis congenita fibroblasts are abnormal and have unbalanced chromosomal rearrangements

Research output: Contribution to journalArticle


I Dokal, J Bungey, P Williamson, D Oscier, J Hows, L Luzzatto

School/Research organisations


Dyskeratosis congenita (DC) is a rare inherited disorder characterized by bone marrow failure, dystrophic changes in the skin and mucous membranes, and a predisposition to malignancy. The DC locus has been mapped to Xq28. The primary defect responsible for this disease remains unknown. We have studied four patients with this disease, three from one family and one from another. In all four patients, primary skin fibroblast cultures were abnormal both in morphology (polygonal cell shape, ballooning, and dendritic-like projections) and in growth rate (doubling time about twice normal). Fibroblast survival studies using four clastogens (bleomycin, diepoxybutane, mitomycin-c, and 4-nitroquinoline-1-oxide) and gamma radiation showed no significant difference between DC and normal fibroblasts. Cytogenetic studies performed on peripheral blood lymphocytes showed no difference between DC and normal lymphocytes with or without prior incubation with clastogens. However, bone marrow metaphases from one of three patients and fibroblasts from two of four patients (who were the eldest of the 4) showed numerous unbalanced chromosomal rearrangements (dicentrics, tricentrics, and translocations) in the absence of any clastogenic agents. Cell-specific differences and a higher rate of chromosomal rearrangements in the older patients appear to correlate with the clinical evolution of the disease. These findings suggest that the DC defect predisposes DC cells to developing chromosomal rearrangements.


Original languageEnglish
Pages (from-to)3090-3096
Issue number12
Publication statusPublished - 15 Dec 1992

Discover related content
Find related publications, people, projects and more using interactive charts.

View graph of relations

Related by author

  1. Non-European doctors and change in UK policy: ten thousand international medical graduates may be affected

    Trewby, P., Williams, G., Williamson, P., Barnes, E., Carr, P., Crilley, J., Foden, A., Mitchell, S. & Murphy, J., 15 Apr 2006, In : British Medical Journal. 332, 7546, p. 913-4 2 p.

    Research output: Contribution to journalLetter

  2. Pohl-Pinkus constrictions of hair following chemotherapy for Hodgkin's disease

    Williamson, P. J. & de Berker, D., Mar 2005, In : British Journal of Haematology. 128, 5, p. 582

    Research output: Contribution to journalLetter

  3. Four pedigrees of the cation-leaky hereditary stomatocytosis class presenting with pseudohyperkalaemia. Novel profile of temperature dependence of Na+–K+ leak in a xerocytic form

    Gore, D. M., Layton, M., Sinha, A. K., Williamson, P. J., Vaidya, B., Connolly, V., Mannix, P., Chetty, M. C., Nicolaou, A. & Stewart, G. W., 19 Apr 2004, In : British Journal of Haematology. 125, 4, p. 521-527 7 p.

    Research output: Contribution to journalArticle

  4. A randomised study comparing an oral regimen with intravenous for consolidation in patients over 55 years with AML in first complete remission

    Jackson, GH., Taylor, PRA., Kaczmarski, R., Mohamed, RJ., Culligan, D., Cullis, J., Littlewood, T., Summerfield, G., Williamson, P. J., Knyba, G. & Samson, D., 2000, In : British Journal of Haematology. 108, supplement

    Research output: Contribution to journalAbstract

  5. Multisystem adverse reaction to lamotrigine

    Schaub, J. E., Williamson, P. J., Barnes, E. W. & Trewby, P. N., 13 Aug 1994, In : Lancet. 344, 8920, p. 481

    Research output: Contribution to journalLetter

Related by journal

  1. Crystal structure of histidine-rich glycoprotein N2 domain reveals redox activity at an interdomain disulfide bridge: implications for angiogenic regulation

    Kassaar, O., McMahon, S. A., Thompson, R., Botting, C. H., Naismith, J. H. & Stewart, A. J., 20 Mar 2014, In : Blood. 123, 12, p. 1948-1955 8 p.

    Research output: Contribution to journalArticle

  2. Regulating type 1 IFN effects in CD8 T cells during viral infections: changing STAT4 and STAT1 expression for function

    Gil, M. P., Ploquin, M. J. Y., Watford, W. T., Lee, S-H., Kim, K., Wang, X., Kanno, Y., O'Shea, J. J. & Biron, C. A., 1 Nov 2012, In : Blood. 120, 18, p. 3718-3728 11 p.

    Research output: Contribution to journalArticle

  3. Modulation of STAT1 protein levels: a mechanism shaping CD8 T-cell responses in vivo

    Gil, MP., Salomon, R., Louten, J. & Biron, CA., 1 Feb 2006, In : Blood. 107, 3, p. 987-993 7 p.

    Research output: Contribution to journalArticle

  4. Lack of evidence for functional ADP-activated human P2X1 receptors supports a role for ATP during hemostasis and thrombosis.

    Vial, C., Pitt, S. J., Roberts, J. A., Rolf, M. G., Mahaut-Smith, M. P. & Evans, R. J., 2003, In : Blood. 102, 10, p. 3646-51

    Research output: Contribution to journalArticle

  5. Somatic I kappa B alpha mutations are a frequent occurrence in Hodgkin lymphoma.

    Jarrett, R. F., Lake, A., Andrew, L., Shield, L., Khan, G., Cabannes, E., Hay, R. T. & Osborne, J., 16 Nov 2002, In : Blood. 100, 1 p.

    Research output: Contribution to journalArticle

ID: 255030415