A Novel EXT1 Mutation Identified in a Family with Multiple Osteochondromas

Multiple exostoses (MO), also referred to as hereditary multiple exostoses (HME), is an autosomal dominant inherited skeletal disorder that has been found to be associated with mutations in the EXT1 and EXT2 genes. In the present study, we report a Chinese family with HME and our mutational analyses of the EXT1 and EXT2 genes in affected and unaffected individuals.

All exons of the EXT1 and EXT2 genes in seven family members were polymerase chain reaction amplified from blood and sequenced.

A heterozygous mutation (c.1056G>T) was identified in exon 2 of the EXT1 gene in the proband and other affected family members; this mutation was not found in the unaffected family members.

This c.1056G>T mutation is located in the exostosin domain of the EXT1 protein and leads to an amino acid change of Glutamine (Gln) to Histidine (His) at position 352. Homology searches reveal that Gln352 is highly conserved in many species and may play an essential role in the normal function of the EXT1 protein.

This study contributes to a better understanding of the genetic basis of HME, expands the known mutational spectrum of EXT1, and provides a reference for genetic counseling and prenatal diagnosis of this family.