GENETIC-HETEROGENEITY IN FAMILIES WITH HEREDITARY MULTIPLE EXOSTOSES

We have carried out a linkage analysis on 11 families segregating gene (s) for hereditary multiple exostoses (EXT). Four highly informative, short tandem-repeat (STR) markers that have been physically mapped to an interval surrounding the Langer-Giedion chromosomal region (8q24.11 -q24.13) were used in a multipoint linkage analysis. Significant evide nce for linkage of EXT with genetic heterogeneity was found. A model o f heterogeneity with linkage of the disease gene to the STR markers in 70% of the families (with a 95% confidence interval of 26%-96%) produ ced a maximum LOD score of 8.11, with the most likely position of EXT between D8S85 and D8S199. Thus there are at least two genes that are c apable of causing hereditary multiple exostoses, one in the Langer-Gie dion region and one at another, unlinked location.