Prenatal diagnosis of xeroderma pigmentosum and trichothiodystrophy in 76 pregnancies at risk

Objective Evaluation of results in a consecutive series of 76 prenatal diagnoses for xeroderma pigmentosum (XP) and trichothiodystrophy (TTD) made since 1977. Methods UV-induced DNA repair synthesis was assessed by the autoradiographic measurement of the incorporation of 3H-thymidine. Results XP was diagnosed in 19 of the 76 investigated pregnancies at risk; cultured chorionic villus (CV) cells were used in 33 pregnancies with ten affected fetuses and cultured amniocytes in 43 pregnancies with nine affected fetuses. In four cases, CVS results were corroborated by subsequent investigation of amniocytes because maternal cell contamination in the CV cell culture was either present or could not be excluded. Uncertain results in two other cases with intermediate DNA repair capacity and severe maternal cell contamination required further investigation. Median time needed for cell culture and analysis was 25 days. To reduce intra-assay variations, a modification of the DNA repair synthesis assay has recently been developed. In this assay, patients and controls are investigated simultaneously in mixed cultures of cells labelled with polystyrene beads. Conclusion Reliable prenatal diagnosis for XP and TTD can be made by the demonstration of clearly reduced UV-induced DNA repair synthesis due to defective global genome nucleotide excision repair. Copyright © 2007 John Wiley & Sons, Ltd.