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.