1. Introduction
Duchenne Muscular Dystrophy (DMD)
is a X‐linked recessive lethal
disorder found in approximately
1/3,500 live male births. The symptoms or signs of the disease is
characterized by early-onset, rapidly progressive muscle degeneration,
muscle weakness, and being wheel-chair-dependent before age 13 and even
dead of cardiopulmonary failure at age 20 (Birnkrant
et al., 2018).
The incidence of DMD is correlated with genetic variants of the DMD
gene, which is one of the biggest genes (OMIM: 310200) on chromosome
Xp.21.2 (Muntoni F, Torelli,
&Ferlini, 2003). The DMD gene spans over 2.22Mb, more than 99% of
which is intronic sequence (Keegan, 2020). The coding sequence of its
largest isoform with totally 11,058 bases across 79 exons harbors a
14kbp transcript encoding a 427 KD protein product
(Keegan, 2020) . The protein is a
major component of the dystrophin-glycoprotein complex that maintains
the structural integrity of the different muscle tissue (such as
skeletal, cardiac and smooth muscles) by linking the muscle contractile
cytoskeleton with the extracellular matrix (Chevron,
Girard, Claustres, &Demaille,
1994). Mutations in the DMD gene usually results in disrupting
the reading frame, responsible of generating truncated/dysfunctional
protein (Monaco, Bertelson,
Liechti-Gallati, Moser, &Kunkel, 1998). Previous reports have
summarized the DMD gene variation spectrum, containing deletion,
duplication, small rearrangement, and point mutation. Large deletion in
the DMD gene has been observed in more than 70% of diagnosed patients,
while large duplication was seen in more than 10% (Ankala, et al.,
2012). Current evidence demonstrated that the deletion spots are usually
identified at exons 45–52 and 8–13 but the gene deletion pattern
differs between cases (Baudat, et
al., 2010). In our study, we found a novel splicing mutation in the
proband, which is not seen in Clinvar or Human Genome database and
undescribed in current clinical reports. The novel splicing mutation
found in the proband was not only detected in the patient’s parents but
also confirmed in a prenatal diagnosis at the second pregnancy of the
patient’s mother; Further, the effect of the splicing mutation on
damaging biofunction of the coded protein was investigated to confirm
its putative role. The findings could be new evidence for diagnosing
prenatal case and for preventing the birth defect incidence since there
is not yet an effective cure of DMD to date (Hirst, McCullagh, &Davies,
2005).