Abstract
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 byDYNC1H1 mutations.
Keywords Neuromuscular diseases, Spinal muscular diseases,
Charcot-Marie-Tooth disease, DYNC1H1 , Genotype-phenotype
correlation