Molecular cloning of a candidate gene for hereditary multiple exostoses type II

Hereditary multiple exostoses (EXT) are an autosomal dominant disorder characterized by multiple exostoses most commonly arising from the juxtaepiphysial region of the long bones. Three genetic loci have been established by cytogenetic abnomality and molecular linkage analysis at 8q24.1 (EXT1), 11p11(EXT2) and 19p(EXT3), respectively. A putative tumor suppressor gene at 8q24.1 was cloned and identified to be responsible for EXT1. With positional cloning approach a gene has been cloned which shares striking similarity with EXT1 gene in both DNA and amino add sequences. This gene is predicted to encode a polypeptide in at least two isoforms, which differ in the middle of the coding region of this gene. The isoform isolated from human placenta cDNA library encodes a polypeptide of 728 amino acids, while the other cloned from human brain cDNA library encodes 718 amino acids. This gene has been mapped by fluorescence in situ hybridization to 11p11, which is the exact region where EXT2 gene is located. The striking DNA similarity and the exact location make this gene a strong candidate responsible for EXT2.