SPLICE-SITE MUTATIONS IN A XERODERMA-PIGMENTOSUM GROUP-A PATIENT WITHDELAYED-ONSET OF NEUROLOGICAL DISEASE

XP12BE is a commonly studied XP-A cell line that exhibits slightly inc reased resistance to UV compared with the majority of XP-A cell lines. The elevated UV survival is common to a subset of XP-A cell lines and correlates with delayed onset of the neurological disease in patients . We identified the XPA mutations in XP12BE by single strand conformat ion polymorphism (SSCP) analyses and nucleotide sequencing. XP12BE is a compound heterozygote and both mutations affect mRNA splicing. One m utation is a G to C transversion within the splice donor site of intro n 4 that is common to several cell lines from XP-A patients with delay ed onset of neurological disease. The other mutation is a G to T trans version at the same position as a G to C transversion in the splice ac ceptor site of intron 3 that is common in Japanese XP-A patients. We a lso demonstrated the persistence of the XP12BE mutations in cell line 2-O-A(2) which has been shown to express XPA protein. These results su ggest that the intron 4 splice donor mutation likely produces some, at least partially functional, XPA protein that accounts for the increas ed UV survival of XP-A cell lines derived from patients with delayed o nset of neurological disease.