A Novel Nonsense Mutation in the EXT2 Gene Identified in a Family with Hereditary Multiple Osteochondromas.

Aims: Identification of genetic mutations linked to hereditary multiple osteochondromas (HMO) is crucial for understanding the molecular mechanisms leading to disease pathogenesis. In this study, we investigated four patients and eight healthy individuals from a family with HMO. Methods: Clinical HMO data and Sanger sequences of the coding regions of the exostosin glycosyltransferase 1 (EXT1) gene (18q24.11) and the EXT2 gene (11p12) of all 12 members of the family were analyzed. Results: A novel nonsense mutation in the EXT2 gene (c.526C>T; p.Gln176*) was detected, which was present in all four patients but absent in their healthy relatives. This mutation encodes a stop codon that results in a truncated EXT2 protein that consists of only 176 amino acids and lacks the remaining 522 amino acids at its C-terminus, missing the entire glycosyltransferase domain. Conclusions: Association of a truncated EXT2 protein with HMO provides new insights into exostosis pathogenesis, highlighting potential roles of the EXT2 gene and its glycosyltransferase domain. Further research is required to understand the mechanisms underlying the development of exostosis.