Although the main causative genes for hereditary multiple exostoses (HME) are exostosin (EXT)‑1 and EXT‑2, there are numerous patients with HME without EXT‑1 and EXT‑2 mutations. The present study aimed to identify novel candidate genes for the development of HME in patients without EXT‑1 and EXT‑2 mutations. Whole‑exome sequencing was performed in a Chinese family with HME and without EXT‑1 and EXT‑2 mutations, followed by a combined bioinformatics pipeline including annotation and filtering processes to identify candidate variants. Candidate variants were then validated using Sanger sequencing. A total of 1,830 original variants were revealed to be heterozygous mutations in three patients with HME which were not present in healthy controls. Two mutations [c.C1849T in solute carrier family 20 member 2 (SLC20A2) and c.G506A in leucine zipper and EF‑hand containing transmembrane protein 1 (LETM1)] were identified as possible causative variants for HME through a bioinformatics filtering procedure and harmful prediction. Sanger sequencing results confirmed these two mutations in all patients with HME. A mutation in SLC20A2 (c.C1849T) led to a change in an amino acid (p.R617C), which may be involved in the development of HME by inducing metabolic disorders of phosphate and abnormal proliferation and differentiation in chondrocytes. In conclusion, the present study revealed two mutations [SLC20A2 (c.C1849T) and LETM1 (c.G506A) in a Chinese family with HME. The mutation in SLC20A2 (c.C1849T)] was more likely to be involved in the development of HME.
Keywords: hereditary multiple exostoses; solute carrier family 20 member 2; mutation; whole-exome sequencing.