Novel deletion and 2397 G>T mutations of the EXT1 gene identified in two Chinese pedigrees with hereditary multiple exostoses using exon sequencing

Background Hereditary multiple exostoses (HME), a rare genetic pediatric disorder, has a peculiar pathogenic mechanism. The results of previous studies have shown that HME is associated with mutations of the EXT1 and EXT2 genes at a molecular genetics level. In our study, two families who received therapy in the Department of Orthopedics of Shanghai Children's Hospital between June, 2017 and November, 2018 were recruited, and a mutational analysis of the EXT1 genes was conducted to further elucidating the relationship between HME and EXT1. Methods Venous blood samples were collected from individuals with HME and their families. Exon sequencing and RT-PCR were performed to comprehensively analyze 11 exons of the EXT1 gene. Results The deletion of exon 7 and the 2397 G>T mutation in exon 7 caused deletion mutation and nonsense mutation only in the HME patients. The mutations in exon 7 were tested and verified by Sanger sequencing. RT-PCR showed that the mRNA expression of EXT1 was significantly decreased in the mutation samples compared with the normal samples, which exerted a great influence on the function of EXT1. Conclusions This study identified new mutation sites for the pathogenesis of HME and further clarified the relationship between HME and EXT1.