Expanding the Phenotypic and Genetic Spectrum of Neuromuscular Diseases
Caused by DYNC1H1 Mutations
Objective: Spinal muscular atrophy, lower limb-dominant (SMA-LED), and
Charcot-Marie-Tooth type 2O (CMT2O) are two kinds of familial
neuromuscular diseases. In this study, we reported two patients with
CMT2O caused by DYNC1H1 mutations and further analyzed the
genotype-phenotype correlations. Methods: Two CMT2O patients and their
parents’ clinical data were collected and genetic analysis was applied.
PubMed, Web of Science, CNKI and Wanfang Data were searched, and all
publications that met the inclusion criteria were carefully screened.
Results: Genetic testing of our two CMT2O patients revealed heterozygous
mutations DYNC1H1 c.1792C>T/p.R598C and
c.790C>G/p.R264G, respectively. Next, a total of 22
original published articles were included and analyzed. Compared to
SMA-LED, CMT2O patients had no proximal-dominant wasting, more
distal-dominant weakness of lower limbs and more sensory abnormalities.
Genotype-phenotype analysis revealed that mutations in the DYN1 region
of DYNC1H1 protein were associated with a more severe phenotype, more
complicated symptoms and more involvement of the central nervous system
than that in the DHC_N1 region. Conclusion: Our findings of the
phenotypic differences between SMA-LED and CMT2O patients provide
references for early diagnosis and differentiation of the two diseases.
The genotype-phenotype correlation may reflect the pathogenesis
underlying dyneinopathy caused by DYNC1H1 mutations.