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Dyskeratosis congenita fibroblasts are abnormal and have unbalanced
chromosomal rearrangements
I Dokal, J Bungey, P Williamson, D Oscier, J Hows and L Luzzatto
Department of Haematology, Royal Postgraduate Medical School, UK.
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.
Volume 80,
Issue 12,
pp. 3090-3096,
12/15/1992
Copyright © 1992 by The American Society of Hematology
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