Novel mutation of EXT2 identified in a large family with multiple osteochondromas

Multiple osteochondromas (MO), also known as hereditary multiple exostoses, is an autosomal dominant bone disorder. Mutations in exostosin glycosyl transferase-1 (EXT1) and exostosin glycosyl transferase-2 (EXT2), including missense, nonsense, frameshift and splice-site mutations, account for up to 80% of reported cases. The proteins EXT1 and EXT2 form a hetero-oligomeric complex that functions in heparan sulfate proteoglycan biosynthesis. A heterozygous EXT2 mutation, c.939+1G>T, was identified in a five-generation 33-member MO family, and was present in all 13 affected members. The mutation results in deletion of exon 5 in the mRNA, producing a frameshift that leads to a premature termination codon. The present study extends the mutational spectrum of EXT2.