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

作者：Xiaohui Duan, Xiaoxuan Liu, Guochun Wang, Weihong Gu, Min Xu, Ying Hao, Mingrui Dong, Qing Sun, Shaojie Sun, Yuanyuan Chen, Wei Wang, Jing Li, Yuting Zhang, Zhenhua Cao, Dongsheng Fan, Renbin Wang, Yuwei Da · 发表于：Orphanet Journal of Rare Diseases · 年份：2021 · DOI：10.1186/s13023-021-01881-7 · 被引用次数：10 · 研究领域：Hereditary Neurological Disorders、Amyotrophic Lateral Sclerosis Research、Peripheral Neuropathies and Disorders

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 wi...