scholarly journals Characterization of genotype–phenotype correlation with MORC2 mutated Axonal Charcot–Marie–Tooth disease in a cohort of Chinese patients

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Xiaohui Duan ◽  
Xiaoxuan Liu ◽  
Guochun Wang ◽  
Weihong Gu ◽  
Min Xu ◽  
...  

Abstract Background Charcot–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. Methods With 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. Results We 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. Conclusions Our 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.

2021 ◽  
Author(s):  
Xiaohui Duan ◽  
Xiaoxuan Liu ◽  
Guochun Wang ◽  
Weihong Gu ◽  
Min Xu ◽  
...  

Abstract Objective Charcot –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. Methods With 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. Results We 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, 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 with the most common mutation c.754C>T p. R252W, 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.Conclusions Our study confirmed that MORC2-related neuropathies exist in the Chinese population, as 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.


2018 ◽  
Vol 63 (10) ◽  
pp. 1041-1048 ◽  
Author(s):  
Ruiyi Yuan ◽  
Junfei Yi ◽  
Zhiying Xie ◽  
Yimeng Zheng ◽  
Miao Han ◽  
...  

2020 ◽  
Vol 50 (11) ◽  
pp. 1306-1315
Author(s):  
Zhong Die Li ◽  
Kuerbanjiang Abuduxikuer ◽  
Jing Zhang ◽  
Ye Yang ◽  
Yi‐Ling Qiu ◽  
...  

2017 ◽  
Vol 92 (1) ◽  
pp. 69-79 ◽  
Author(s):  
N. Cheng ◽  
H. Wang ◽  
W. Wu ◽  
R. Yang ◽  
L. Liu ◽  
...  

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