loading page

Expanding the Phenotypic and Genetic Spectrum of Neuromuscular Diseases Caused by DYNC1H1 Mutations
  • Jia-Tong Li,
  • Si-qi Dong,
  • Xiangjun Chen
Jia-Tong Li
Huashan Hospital Fudan University
Author Profile
Si-qi Dong
Huashan Hospital Fudan University
Author Profile
Xiangjun Chen
Huashan Hospital Fudan University
Author Profile


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.

Peer review status:UNDER REVIEW

17 May 2021Submitted to Human Mutation
21 May 2021Assigned to Editor
21 May 2021Submission Checks Completed
04 Jun 2021Reviewer(s) Assigned