Abstract for presentation at 11th International Congress of Human Genetics

Purpose: Xeroderma pigmentosum (XP) is a rare disorder that is characterized by extreme sensitivity to UV-light. UV-light exposure results in the formation of cyclobutane dimers and (6-4) photoproducts. Nucleotide excision repair (NER) orchestrates the removal of cyclobutane dimers and (6-4) photoproducts as well as some forms of bulky chemical DNA adducts. The disease XP is comprised of 7 complementation groups, which represent functional deficiencies in seven different genes, all of which are involved in NER. Several of the XP complementation groups exhibit neurological symptoms in addition to the extreme sensitivity to UV-light. This study focused on identifying altered gene expression related to the presence of neurological symptoms in XP.
Methods: 7 cell lines were treated with UV-light and 6000 gene cDNA microarray analysis was performed in duplicate for each cell line.
Results: A graded change in gene expression pattern between the mildest and severest forms of the disease was identified with the mildest form represented by XPE, which is most similar to the control response and XPA representing the severest for of the disease being distinctly different to control cells. The most striking observation was the identification of a subset of genes that were significantly different in their expression profiles in the cells derived from those XP complementation groups associated with severe neurological abnormalities (XPA, XPD and XPG) compared to those that do not (XPC, XPE, XPF).
Conclusions: Gene expression profiles identified for each XP complementation group and the identification of genes with altered expression in relation to neurological symptoms may be of value in the diagnosis of the disease.