3. Results
3.1 Likely genetic variations associated with HME
The exons of the EXT1, EXT2 and the other 59 genes associated with HME (recommended by American College of Medical Genetics and Genomics, ACMG SF v2.0, shown in Table 1 ) (Kalia et al., 2017) were screened in the proband (Ⅲ-3) to reveal the possible pathogenic gene variants of HME. No mutations were discovered in the EXT2 and the other 59 genes. However, a heterozygous frameshift insertion mutation in exon 1 of the EXT1 gene was detected (c.325dup), which was predicted to cause the early termination of protein translation (Fig.2A ). We also screened the HME associated genes for the other family members, including affected individuals (Ⅱ-1, Ⅱ-5 and Ⅲ-1) and unaffected individuals (Ⅰ-2, Ⅱ-2, Ⅱ-3, Ⅱ-4, Ⅱ-6 and Ⅲ-2). The heterozygous frameshift insertion mutation of the proband was also detected in the affected family members but not in the unaffected family members (Fig.2B and Fig.2C) .
We examined the reported gene variants of EXT1 gene in Human Gene Mutation Database (HGMD) (shown in Table 2 ). The heterozygous frameshift insertion mutation identified in our study was absent in HGMD, thus it is recognized as a new gene variant associated with HME.
Table 1. 59 genes associated with HME were listed in ACMG SF v2.0