IDENTIFICATION OF NOVEL MUTATIONS IN THE HUMAN EXT1 TUMOR-SUPPRESSOR GENE

Hereditary multiple exostoses (EXT) is a genetically heterogeneous bon e disorder caused by genes segregating on human chromosomes 8, 11, and 19 and designated EXT1, EXT2 and EXT3, respectively. Recently, the EX T1 gene has been isolated and partially characterized and appears to e ncode a tumor suppressor gene. We have identified six mutations in the human EXT1 gene from six unrelated multiple exostoses families segreg ating for the EXT gene on chromosome 8. One of the mutations we detect ed is the same l-bp deletion in exon 6 that was previously reported in two independent EXT families. The other five mutations, in exons 1, 6 , 9, and the splice junction at the 3' end of exon 2, are novel. In ea ch case, the mutation is likely to result in a truncated or nonfunctio nal EXT1 protein. These results corroborate and extend the previous re port of mutations in this gene in two EXT families, and provide additi onal support for the EXT1 gene as the cause of hereditary multiple exo stoses in families showing linkage to chromosome 8.