GENETIC-ANALYSIS OF 22 PATIENTS WITH COCKAYNE-SYNDROME

Cockayne syndrome (CS) is an autosomal recessive disorder with dwarfis m, mental retardation, sun sensitivity and a variety of other features . Cultured CS cells are hypersensitive to ultraviolet (UV) light, and following UV irradiation, CS cells are unable to restore RNA synthesis rates to normal levels. This has been attributed to a specific defici ency in CS cells in the ability to repair damage in actively transcrib ed regions of DNA at the rapid rate seen in normal cells. We have used the failure of recovery of RNA synthesis, following UV irradiation of C cells, in a complementation test. Cells of different CS donors are fused. Restoration of normal RNA synthesis rates in UV-irradiated hete rodikaryons indicates that the donors are in different complementation groups, whereas a failure to effect this recovery implies that they a re in the same group. In an analysis of cell strains from 22 CS donors from several countries and different racial groups. we have assigned five cell strains to the CS-A group and the remaining 17 to CS-B, No o bvious racial, clinical or cellular distinctions could be made between individuals in the two groups. Our analysis will assist the identific ation of mutations in the recently cloned CSA and CSB genes and the st udy of structure-function relationships.