XERODERMA-PIGMENTOSUM COMPLEMENTATION GROUP-G ASSOCIATED WITH COCKAYNE-SYNDROME

Xeroderma pigmentosum (XP) and Cockayne syndrome (CS) are two rare inh erited disorders with a clinical and cellular hypersensitivity to the UV component of the sunlight spectrum. Although the two traits are gen erally considered as clinically and genetically distinct entities, on the biochemical level a defect in the nucleotide excision-repair (NER) pathway is involved in both. Classical CS patients are primarily defi cient in the preferential repair of DNA damage in actively transcribed genes, whereas in most XP patients the genetic defect affects both '' preferential'' and ''overall'' NER modalities. Here we report a geneti c study of two unrelated, severely affected patients with the clinical characteristics of CS but with a biochemical defect typical of XP. By complementation analysis, using somatic cell fusion and nuclear micro injection of cloned repair genes, we assign these two patients to XP c omplementation group G, which previously was not associated with CS. T his observation extends the earlier identification of two patients wit h a rare combined XP/CS phenotype within XP complementation groups B a nd D, respectively. It indicates that some mutations in at least three of the seven genes known to be involved in XP also can result in a pi cture of partial or even full-blown CS. We conclude that the syndromes XP and CS are biochemically closely related and may be part of a broa der clinical disease spectrum. We suggest, as a possible molecular mec hanism underlying this relation, that the XPGC repair gene has an addi tional vital function, as shown for some other NER genes.