A novel mutation of EXT gene in a pedigree with hereditary multiple exostoses

Objective To investigate EXT gene sequence in a pedigree with hereditary multiple exostoses (HME) and identify the causative mutation in the pedigree. Methods All the exons and their flanking sequences of EXT1 and EXT2 genes were amplified by PCR from proband′ s genomic DNA, PCR products were purified and sent for direct sequencing. Results A novel insertion-deletion (651 - 664 delins TTT) mutation in exon 1 of EXT1 gene was found, the mutation resulted in a frameshift at amino acid position 218 and a premature stop codon at position 220 (K218 fs X220) in the EXT1 protein. The mutation also lead to a truncated protein. Family study results showed that this mutation came from the proband′s mother. No variant was found in EXT2 gene of this proband. Conclusions 651 - 664 delins TTT heterozygous mutation in EXT1 gene was the molecular mechanism of HME for this pedigree.