Clinical and genetic features of a cohort of patients with MFN2-related neuropathy.
Clinical and genetic features of a cohort of patients with MFN2-related neuropathy.
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MFN 2相关神经病变患者队列的临床和遗传特征
DOI：
10.1038/s41598-022-10220-0
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发表时间：
2022-04-13
影响因子：
4.6
通讯作者：
Corti, Stefania
中科院分区：
文献类型：
--
作者：
Abati, Elena;Manini, Arianna;Velardo, Daniele;Del Bo, Roberto;Napoli, Laura;Rizzo, Federica;Moggio, Maurizio;Bresolin, Nereo;Bellone, Emilia;Bassi, Maria Teresa;D'Angelo, Maria Grazia;Comi, Giacomo Pietro;Corti, Stefania
腓骨肌萎缩症2A型（Charcot-Marie-Tooth disease type 2A，CMT 2A）是一种罕见的遗传性轴索神经病，由MFN 2基因突变引起。我们对来自10个家族的13名携带MFN 2突变的患者进行了横断面分析，描述了他们的临床和遗传特征。评价的患者表现出不同的发病年龄和广泛的表型谱，大多数患者表现出严重的表型。检测到一种新的杂合错义变体，p.K357E。它位于高度保守的位置，并通过计算机工具预测为致病性。在临床水平上，p.K357E携带者表现出严重的感觉运动轴突神经病。总之，我们的工作扩展了CMT 2A的遗传谱，揭示了一种新的突变及其相关的临床效应，并详细描述了MFN 2突变患者队列的临床特征。在受影响的家庭中获得精确的遗传诊断对于计划生育和产前诊断至关重要，并且从治疗的角度来看，因为我们正在进入遗传疾病个性化治疗的时代。
Charcot–Marie–Tooth disease type 2A (CMT2A) is a rare inherited axonal neuropathy caused by mutations in MFN2 gene, which encodes Mitofusin 2, a transmembrane protein of the outer mitochondrial membrane. We performed a cross-sectional analysis on thirteen patients carrying mutations in MFN2, from ten families, describing their clinical and genetic characteristics. Evaluated patients presented a variable age of onset and a wide phenotypic spectrum, with most patients presenting a severe phenotype. A novel heterozygous missense variant was detected, p.K357E. It is located at a highly conserved position and predicted as pathogenic by in silico tools. At a clinical level, the p.K357E carrier shows a severe sensorimotor axonal neuropathy. In conclusion, our work expands the genetic spectrum of CMT2A, disclosing a novel mutation and its related clinical effect, and provides a detailed description of the clinical features of a cohort of patients with MFN2 mutations. Obtaining a precise genetic diagnosis in affected families is crucial both for family planning and prenatal diagnosis, and in a therapeutic perspective, as we are entering the era of personalized therapy for genetic diseases.
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DOI：
10.1111/j.1529-8027.2011.00350.x
发表时间：
2011-09
期刊：
Journal of the peripheral nervous system : JPNS
影响因子：
--
作者：
Murphy SM;Herrmann DN;McDermott MP;Scherer SS;Shy ME;Reilly MM;Pareyson D
通讯作者：
Pareyson D
影响因子：
--
作者：
Engelfried, Kathrin;Vorgerd, Matthias;Hagedorn, Michaela;Haas, Gerhard;Gilles, Juergen;Epplen, Joerg T.;Meins, Moritz
通讯作者：
Meins, Moritz
影响因子：
7.8
作者：
Detmer, Scott A;Chan, David C
通讯作者：
Chan, David C
影响因子：
9.9
作者：
Fridman, Vera;Sillau, Stefan;Shy, Michael E.
通讯作者：
Shy, Michael E.
DOI：
10.1083/jcb.200211046
发表时间：
2003-01-20
期刊：
The Journal of cell biology
影响因子：
--
作者：
Chen H;Detmer SA;Ewald AJ;Griffin EE;Fraser SE;Chan DC
通讯作者：
Chan DC