Validation of XP-C pathogenic variations in archival material from a live XP patient

Abstract

Xeroderma pigmentosum (XP) genetic complementation group C (XP-C) is the most common form of the disease worldwide. Thirty-four distinct genetic defects have been identified in 45 XP-C patients. Further identification of such defects and the frequency of their occurrence offers the potential of generating diagnostic and prognostic molecular screening panels. Archival material (such as formalin-fixed paraffin embedded skin) may be useful for the identification of novel genetic variations and for documenting the frequency of individual genetic defects in patients who are no longer available for study. However, the use of archival material precludes direct analysis of changes in the mRNA resulting from genomic changes. The serendipitous reacquisition of an XP individual in whom genetic defects were previously characterized in archival material allowed confirmation of the defects as well as a direct analysis of the consequences of these defects on mRNA, mRNA expression and on cellular phenotypes.