Xeroderma pigmentosum: a rapid sensitive method for prenatal diagnosis.

When normal human cells, capable of repairing ultraviolet-induced lesions in their DNA, are incubated in the thymidine analog 5-bromodeoxyuridine after ultraviolet irradiation, the analog is incorporated into the repaired regions. When such repaired cells are subsequently irradiated with 313-nanometer radiation and placed in alkali, breaks appear in the DNA at sites of incorporation of 5bromodeoxyuridine, inducing a dramatic downward shift in the sedimentation constant of the DNA. Cells from patients with the disease xeroderma pigmentosum, which causes sensitivity to ultraviolet, are incapable or only minimally capable of repair; such cells incorporate little 5-bromodeoxyuridine into their DNA under these conditions and, upon 313-nanometer irradiation and sedimentation in alkali, exhibit only minor shifts in DNA sedimentation constants. When fibroblasts developed from biopsies of normal skin and of skin from patients with xeroderma pigmentosum, as well as cells cultured from midtrimester amniotic fluid, were assayed in this fashion unequivocal differences between normal and xeroderma pigmentosum cells were shown. Xeroderma pigmentosum heterozygotes are clearly distinguishable from homozygous mutants, and results are available 12 hours after irradiation.