Enhanced G2 chromatid radiosensitivity in dyskeratosis congenita fibroblasts

Am J Hum Genet. 1990 Feb;46(2):350-7.


Dyskeratosis congenita (DC) is an inherited disorder characterized by reticular pigmentation of the skin, dystrophic nails, mucosal leukoplakia, and a predisposition to cancer in early adult life. In the majority of cases, DC is an X-linked recessive trait. However, one or more autosomal form(s) of DC may exist. Although excessive spontaneous chromatid breakage has been reported in DC, it is not a consistent cytological marker for this disorder. We examined the frequency and specificity of X-irradiation-induced G2 chromatid breakage in fibroblasts from three unrelated DC patients (two males and one female). Metaphase cells from DC patients had significantly more chromatid breaks (16-18-fold and 17-26-fold at 50 and 100 rad X-irradiation, respectively) and chromatid gaps (10-12-fold and 6-7-fold at 50 and 100 rad, respectively) than those from two different controls. Analysis of banded chromosomes revealed a nonrandom distribution of chromatid aberrations in DC but not in controls, a distribution corresponding to some of the known breakpoints for cancer-specific rearrangements, constitutive fragile sites, and/or loci for cellular proto-oncogenes. The significance of this finding for cancer predisposition in DC patients is uncertain, but the increased susceptibility of X-irradiation-induced chromatid breakage may serve as a cellular marker of diagnostic value.

MeSH terms

  • Cell Line
  • Chromatids / radiation effects*
  • Chromosome Aberrations*
  • Chromosome Fragile Sites
  • Chromosome Fragility
  • Female
  • Fibroblasts / radiation effects
  • Humans
  • Interphase
  • Male
  • Metaphase
  • Pigmentation Disorders / congenital
  • Pigmentation Disorders / genetics*
  • X-Rays