Background: Multiple osteochondroma (MO) is an autosomal dominant skeletal disorder characterized by the formation of multiple osteochondromas, and exostosin-1 (EXT1) and exostosin-2 (EXT2) are major causative genes in MO. In this study, we evaluated the genetic backgrounds and mutational patterns in Japanese families with MO. Results: We evaluated 112 patients in 71 families with MO. Genomic DNA was isolated from peripheral blood leucocytes. The exons and exon/intron junctions of EXT1 and EXT2 were directly sequenced after PCR amplification. Fifty-two mutations in 47 families with MO in either EXT1 or EXT2, and 42.3 % (22/52) of mutations were novel mutations. Twenty-nine families (40.8 %) had mutations in EXT1, and 15 families (21.1 %) had mutations in EXT2. Interestingly, three families (4.2 %) had mutations in both EXT1 and EXT2. Twenty-four families (33.8 %) did not exhibit mutations in either EXT1 or EXT2. With regard to the types of mutations identified, 59.6 % of mutations were inactivating mutations, and 38.5 % of mutations were missense mutations. Conclusions: We found that the prevalence of EXT1 mutations was greater than that of EXT2 mutations in Japanese MO families. Additionally, we identified 22 novel EXT1 and EXT2 mutations in this Japanese MO cohort. This study represents the variety of genotype in MO.
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