中国人群MORC2基因相关神经病的基因变异和临床表现分析
The genetic and clinical features of MORC2 gene-related neuropathy in Chinese patients
周淋 1王梦丽 1曹婉芊 1黄顺祥 1赵华栋 1李陆 1曾森 1张如旭1
作者信息
- 1. 中南大学湘雅三医院神经内科,长沙 410013
- 折叠
摘要
目的 总结中国人群MORC2基因相关神经病的基因变异谱和临床特点.方法 收集2010-2023年就诊于中南大学湘雅三医院并明确基因诊断的MORC2基因相关神经病家系的临床资料和全外显子测序结果,回顾性分析其基因变异和临床特点,并查阅已报道的中国MORC2基因相关神经病家系相关文献,对中国人群该疾病的基因变异和临床表型谱进行总结.结果 本中心收集的10个家系共携带6个不同的MORC2基因杂合致病变异,其中c.1330G＞C(p.G444R)为新报道的变异.6个家系表现为儿童期或成年期起病的MORC2基因变异所致的轴索型腓骨肌萎缩症(CMT2Z)表型,携带 c.754C＞T(p.R252W)、c.1199A＞G(p.Q400R)、c.1330G＞C(p.G444R)或 c.1396G＞A(p.D466N);3个家系表现为婴幼儿起病、严重的脊髓性肌萎缩(SMA)样表型,均携带c.260C＞T(p.S87L);1个家系表现为婴幼儿起病、以智能和运动发育迟缓为主要表现的DIGFAN综合征,携带c.1181A＞G(p.Y394C).文献复习发现8个携带MORC2基因致病变异的中国家系,其中5个家系表现为 CMT2Z 表型,携带 c.754C＞T(p.R252W)、c.1079A＞G(p.E360G)、c.1220G＞A(p.C407Y)或c.1397A＞G(p.D466G);1个家系为SMA样表型,携带c.260C＞T(p.S87L);2个家系表现为DIGFAN综合征,分别携带c.79G＞A(p.E27K)和c.292G＞A(p.G98R).结论 本研究报道了 CMT2表型相关的MORC2基因新致病变异c.1330G＞C(p.G444R).在中国人群中,迄今共报道11个MORC2基因致病变异,c.754C＞T(p.R252W)可能为最常见致病变异.MORC2基因相关神经病具有明显的临床异质性,不同变异可表现为CMT2Z、早发严重的SMA样肌无力或DIGFAN综合征.
Abstract
Objective To summarize the genetic and phenotypic features of MORC family CW-type zinc finger 2(MORC2)gene-related neuropathy in Chinese patients.Methods The clinical and whole exome sequencing data of MORC2 gene-related neuropathy families with a definitive genetic diagnosis were collected from the Third Xiangya Hospital of Central South University between 2010 and 2023.Literature involving Chinese families with MORC2 gene-related neuropathy was extensively reviewed to provide a comprehensive summary of the genetic and phenotypic spectrum of the disease.Results A total of 10 families with MORC2 gene-related neuropathy were identified and analyzed.Six different heterozygous pathogenic variants in the MORC2 gene were observed among these families,including the novel variant c.1330G＞C(p.G444R)that had not been previously reported.Six families presented as axonal Charcot-Marie-Tooth disease caused by variants in the MORC2 gene(CMT2Z)phenotype with childhood or adult onset,and carried variants c.754C＞T(p.R252W),c.1199A＞G(p.Q400R),c.1330G＞C(p.G444R),or c.1396G＞A(p.D466N);3 families manifested as severe spinal muscular atrophy(SMA)-like phenotype with infantile onset,all carried c.260C＞T(p.S87L);1 family carried c.1181A＞G(p.Y394C),presented as DIGFAN syndrome phenotype with infantile onset combined with mental and motor retardation.Systematic review showed 8 Chinese families carried pathogenic variants of the MORC2 gene,among which 5 families were associated with the CMT2Z phenotype,carrying c.754C＞T(p.R252W),c.1079A＞G(p.E360G),c.1220G＞A(p.C407Y),or c.1397A＞G(p.D466G);1 family was associated with SMA-like phenotype,carrying c.260C＞T(p.S87L);and 2 families were associated with DIGFAN syndrome,carrying c.79G＞A(p.E27K)and c.292G＞A(p.G98R).Conclusions A novel pathogenic variant c.1330G＞C(p.G444R)of the MORC2 gene associated with the CMT2 phenotype is reported.Eleven pathogenic variants of the MORC2 gene have been reported in the Chinese patients to date,and c.754C＞T(p.R252W)may be the most common.Patients with MORC2 gene-related neuropathy carrying different variants present with significant clinical heterogeneity,manifesting as CMT2Z,early-onset severe SMA-like myasthenia,or DIGFAN syndrome.
关键词
夏科-马里-图斯病/肌萎缩,脊髓性/基因变异/MORC2基因Key words
Charcot-Marie-Tooth disease/Muscular atrophy,spinal/Genetic variation/MORC2gene引用本文复制引用
基金项目
国家自然科学基金(81771366)
国家自然科学基金(82171172)
湖南省自然科学基金面上项目(2022JJ30910)
出版年
2024
NETL
NSTL
万方数据