Whole-exome sequencing identified a novel mutation of SLC20A2 (c.C1849T) in a Chinese family with hereditary multiple exostoses

Abstract Background: Although the main causative genes for hereditary multiple exostoses (HME) are EXT-1 and EXT-2, there are still many HME patients without EXT-1 and EXT-2 mutations. This study aimed to identify novel candidate genes for the development of HME in patients without EXT-1 and EXT-2 mutations. Methods: Whole-exome sequencing was performed in a typical Chinese HME family without EXT-1 and EXT-2 mutations, followed by a combined bioinformatics pipeline including annotation and filtering process to identify candidate variants. Candidate variants were then validated by Sanger sequencing. Results: A total of 1830 original variants were revealed to be heterozygous mutations in the three patients suffering from HME that were not present in the healthy controls. Two mutations (c.C1849T in SLC20A2 and c.G506A in LETM1) were identified as a possible causative variant 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 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. Conclusions: The present study revealed two mutations [SLC20A2 (c.C1849T) and LETM1 (c.G506A) in a Chinese HME family. The mutation in SLC20A2 (c.C1849T) is more likely to be involved in the development of HME.