| Title | Characterization of genotype-phenotype correlation with MORC2 mutated Axonal Charcot-Marie-Tooth disease in a cohort of Chinese patients |
| Authors | Duan, Xiaohui Liu, Xiaoxuan Wang, Guochun Gu, Weihong Xu, Min Hao, Ying Dong, Mingrui Sun, Qing Sun, Shaojie Chen, Yuanyuan Wang, Wei Li, Jing Zhang, Yuting Cao, Zhenhua Fan, Dongsheng Wang, Renbin Da, Yuwei |
| Affiliation | China Japan Friendship Hosp, Dept Neurol, Beijing 100029, Peoples R China Peking Univ Third Hosp, Dept Neurol, Beijing 100191, Peoples R China China Japan Friendship Hosp, Dept Rheumatol & Immunol, Beijing 100029, Peoples R China Capital Med Univ, Xuanwu Hosp, Dept Neurol, Chang Chun St, Beijing 100053, Peoples R China China Japan Friendship Hosp, Dept Clin Res Inst, Beijing 100029, Peoples R China Running Gene Inc, Beijing 100191, Peoples R China |
| Keywords | GENE MUTATIONS DIMERIZATION VARIANTS DYNAMICS |
| Issue Date | 31-May-2021 |
| Publisher | ORPHANET JOURNAL OF RARE DISEASES |
| Abstract | BackgroundCharcot-Marie-Tooth (CMT) disease is an exciting field of study, with a growing number of causal genes and an expanding phenotypic spectrum. The microrchidia family CW-type zinc finger 2 gene (MORC2) was newly identified as a causative gene of CMT2Z in 2016. We aimed to describe the phenotypic-genetic spectrum of MORC2-related diseases in the Chinese population.MethodsWith the use of Sanger sequencing and Next Generation Sequencing (NGS) technologies, we screened a cohort of 284 unrelated Chinese CMT2 families. Pathogenicity assessments of MORC2 variants were interpreted according to the ACMG guidelines. Potential pathogenic variants were confirmed by Sanger sequencing.ResultsWe identified 4 different heterozygous MORC2 mutations in four unrelated families, accounting for 1.4% (4/284). A novel mutation c.1397A>G p. D466G was detected in family 1 and all affected patients presented with later onset axonal CMT with hyperCKemia. The patient in family 2 showed a spinal muscular atrophy (SMA)-like disease with cerebellar hypoplasia and mental retardation, with a hot spot de novo mutation c.260C>T p. S87L. The twin sisters in family 3 were identified as having the most common mutation c.754C>T p. R252W and suffered from axonal motor neuropathy with high variability in disease severity and duration. The patient in family 4 developed an early onset axonal motor and sensory neuropathy, with a reported mutation c.1220G>A p.C407Y. All identified mutations associated with MORC2-related neuropathies are localized in the N-terminal ATPase module.ConclusionsOur study confirmed that MORC2-related neuropathies exist in the Chinese population at a relatively high mutation rate. We revealed a complex genotype-phenotype correlation with MORC2 mutations. This report adds a new piece to the puzzle of the genetics of CMT and contributes to a better understanding of the disease mechanisms. |
| URI | http://hdl.handle.net/20.500.11897/622672 |
| DOI | 10.1186/s13023-021-01881-7 |
| Indexed | SCI(E) |
| Appears in Collections: | 第三医院 |
