• Xigui Long, Zhuo Li, Yanru Huang, Li Zhang, Weigang Lv, Yanling Teng, Siyuan Linpeng, Desheng Liang, and Lingqian Wu.
• Center for Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University.
• Medicine (Baltimore). 2019 May 1; 98 (20): e15692e15692.

RationaleHereditary multiple exostoses (HMEs) is an autosomal dominant skeletal disorder.Patient ConcernsSix probands of the 6 unrelated Han Chinese families were identified as having HME. These patients had exostoses at multiple sites and significantly affected joints malformation and movement.DiagnosesHereditary multiple exostoses.InterventionsTo detect the genetic mechanism of HME in 6 unrelated Chinese families, whole-exome sequencing (WES) and multiplex ligation-dependent probe amplification (MLPA) were used after genomic DNA was isolated from peripheral blood leucocytes. Point mutations identified by these methods were verified by Sanger sequencing after PCR amplification.OutcomesSix mutations in the EXT1 and EXT2 genes were identified, including a heterozygous deletion mutation from exon 2 to exon 8 (Family 1), a c.448C>T, p.(Gln150X) heterozygous nonsense mutation (Family 4), a c.1057-2A>T heterozygous splicing substitution (Family 5), and a c.1468dupC, p.(Leu490fs519X) (Family 6) heterozygous duplication mutation in the EXT1 gene in addition to a heterozygous deletion mutation from exon 2 to exon 3 (Family 2) and a c.1197C>G, p.(Tyr399X) heterozygous nonsense mutation (Family 3) in the EXT2 gene.LessonsOverall, we identified 5 novel mutations and 1 recurrent mutation in the EXT1 and EXT2 genes in 6 Chinese families with HME. Our findings expand the mutational spectrum of the EXT1 and EXT2 genes and are useful for genetic counseling and prenatal diagnosis.

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