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