Genetic and Clinical Features in 24 Chinese Distal Hereditary Motor Neuropathy Families.
Genetic and Clinical Features in 24 Chinese Distal Hereditary Motor Neuropathy Families.
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24个中国远端遗传性运动神经病家系的遗传和临床特征
DOI：
10.3389/fneur.2020.603003
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发表时间：
2020
影响因子：
3.4
通讯作者：
Zhang R
中科院分区：
文献类型：
--
作者：
Xie Y;Lin Z;Pakhrin PS;Li X;Wang B;Liu L;Huang S;Zhao H;Cao W;Hu Z;Guo J;Shen L;Tang B;Zhang R
背景和目的：远端遗传性运动神经病（dHMN）是一组临床和遗传异质性遗传性神经病。本研究的目的是报告中国队列中dHMN患者的临床和遗传特征。目的和方法：我们对来自中国大陆的24个dHMN家系进行了临床评估和全外显子组测序。我们对这些数据进行了回顾性分析，并调查了确诊突变患者的频率和临床特征。结果如下：在加尔斯中发现了两个新的杂合突变，c.373 G>C（p.E125 Q）和c.1015 G>A（p.G339 R），它们对应于典型的dHMN-V表型。加上WARS、SORD、SIGMAR 1和HSPB 1突变的家族，29.2%（7/24）的家族获得了明确的遗传诊断。在1例轻度dHMN表型患者中发现了一种新的意义不明的杂合变异体，即LRSAM 1中的c.1834G>A（p.G612S）。结论：我们的研究扩大了加尔斯突变的突变谱，并增加了加尔斯突变与轴突Charcot-Marie-Tooth和dHMN表型相关的证据。氨基酰胺tRNA合成酶（ARS）基因突变可能是常染色体显性dHMN的常见病因，SORD基因突变可能是常染色体隐性dHMN的主要病因。相对较低的基因诊断率表明，更多的致病基因需要发现。
Background and Objectives: Distal hereditary motor neuropathy (dHMN) is a clinically and genetically heterogeneous group of inherited neuropathies. The objectives of this study were to report the clinical and genetic features of dHMN patients in a Chinese cohort. Aims and Methods: We performed clinical assessments and whole-exome sequencing in 24 dHMN families from Mainland China. We conducted a retrospective analysis of the data and investigated the frequency and clinical features of patients with a confirmed mutation. Results: Two novel heterozygous mutations in GARS, c.373G>C (p.E125Q) and c.1015G>A (p.G339R), were identified and corresponded to the typical dHMN-V phenotype. Together with families with WARS, SORD, SIGMAR1, and HSPB1 mutations, 29.2% of families (7/24) acquired a definite genetic diagnosis. One novel heterozygous variant of uncertain significance, c.1834G>A (p.G612S) in LRSAM1, was identified in a patient with mild dHMN phenotype. Conclusion: Our study expanded the mutation spectrum of GARS mutations and added evidence that GARS mutations are associated with both axonal Charcot-Marie-Tooth and dHMN phenotypes. Mutations in genes encoding aminoamide tRNA synthetase (ARS) might be a frequent cause of autosomal dominant-dHMN, and SORD mutation might account for a majority of autosomal recessive-dHMN cases. The relatively low genetic diagnosis yield indicated more causative dHMN genes need to be discovered.
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SORD 的双等位基因突变会导致一种常见且可治疗的遗传性神经病，对糖尿病有影响
影响因子：
30.8
作者：
Cortese A;Zhu Y;Rebelo AP;Negri S;Courel S;Abreu L;Bacon CJ;Bai Y;Bis-Brewer DM;Bugiardini E;Buglo E;Danzi MC;Feely SME;Athanasiou-Fragkouli A;Haridy NA;Inherited Neuropathy Consortium;Isasi R;Khan A;Laurà M;Magri S;Pipis M;Pisciotta C;Powell E;Rossor AM;Saveri P;Sowden JE;Tozza S;Vandrovcova J;Dallman J;Grignani E;Marchioni E;Scherer SS;Tang B;Lin Z;Al-Ajmi A;Schüle R;Synofzik M;Maisonobe T;Stojkovic T;Auer-Grumbach M;Abdelhamed MA;Hamed SA;Zhang R;Manganelli F;Santoro L;Taroni F;Pareyson D;Houlden H;Herrmann DN;Reilly MM;Shy ME;Zhai RG;Zuchner S
通讯作者：
Zuchner S
影响因子：
64.8
作者：
He W;Bai G;Zhou H;Wei N;White NM;Lauer J;Liu H;Shi Y;Dumitru CD;Lettieri K;Shubayev V;Jordanova A;Guergueltcheva V;Griffin PR;Burgess RW;Pfaff SL;Yang XL
通讯作者：
Yang XL
甘氨酰-tRNA 合成酶与 tRNA 复合物的共晶结构表明甘氨酰化存在多种构象状态
影响因子：
4.8
作者：
Qin, Xiangjing;Hao, Zhitai;Xie, Wei
通讯作者：
Xie, Wei
影响因子：
14.9
作者：
Blocquel D;Li S;Wei N;Daub H;Sajish M;Erfurth ML;Kooi G;Zhou J;Bai G;Schimmel P;Jordanova A;Yang XL
通讯作者：
Yang XL
影响因子：
16.2
作者：
Seburn, Kevin L.;Nangle, Leslie A.;Burgess, Robert W.
通讯作者：
Burgess, Robert W.