SOMATIC-CELL HYBRIDIZATION OF ROBERTS SYNDROME AND NORMAL LYMPHOBLASTS RESULTING IN CORRECTION OF BOTH THE CYTOGENETIC AND MUTAGEN HYPERSENSITIVITY CELLULAR PHENOTYPES

Roberts syndrome (RS) is a rare recessive condition of limb deformities, growth retardation, and developmental delay. Cultured cells from approximately half of RS patients exhibit a "puffing" of the constitutive heterochromatin and a hypersensitivity to mitomycin C (MMC). Patients exhibiting these cellular phenomena are designated RS+. Somatic cell hybridization with normal cells has been shown to correct the heterochromatin abnormality in RS+ cells. To determine if the MMC hypersensitivity could also be corrected by hybridization to normal cells, we fused two different RS+ lymphoblastoid cell lines (LCLs) to a ouabain-resistant, HAT-sensitive, normal LCL. Cytogenetic analyses of hybrid cell lines (HCLs) revealed complete correction of the heterochromatin abnormality. MMC cell killing assays revealed correction of the mutagen hypersensitivity as well. Five of the six HCLs tested exhibited D10 values (the dose at which 10% of the cells survive) that were not significantly lower than that of the normal parent but that were 6- to 18-fold greater than those of the RS+ parents. Correction of both of these cellular phenotypes in RS+ cells by fusion with normal cells supports the hypothesis that both of these phenomena are caused by a common defect in the Roberts syndrome gene (RBS).