Case report: Asp194Ala variant in MFN2 is associated with ALS-FTD in an Italian family.
Case report: Asp194Ala variant in MFN2 is associated with ALS-FTD in an Italian family.
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病例报告：Mfn2基因Asp194Ala变异与一个意大利家系ALS-FTD相关。
DOI：
10.3389/fgene.2023.1235887
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发表时间：
2023
影响因子：
3.7
通讯作者：
Pellecchia, M. T.
中科院分区：
文献类型：
--
作者：
Vinciguerra, C.;Di Fonzo, A.;Monfrini, E.;Ronchi, D.;Cuoco, S.;Piscosquito, G.;Barone, P.;Pellecchia, M. T.
关键词：
背景：MFN2基因编码蛋白Mitofusin 2，参与线粒体的基本功能，如融合、运输、周转和细胞相互作用。我们描述了一个携带新型MFN2突变的家庭，该突变与母亲的als -额颞叶痴呆（FTD）临床表型和儿子的charco - marie - tooth病2A型（CMT2A）相关。病例介绍：患者的母亲，67岁，因三年的情绪障碍和步态障碍病史，以及最近的发音减退、构音障碍、吞咽困难和弥漫性肌肉萎缩而向我们就诊。家族病史为精神障碍和步态障碍阳性。脑18F-FDG PET显示双侧额颞叶皮质严重代谢低下。电诊断研究（EDX）显示严重的运动轴索病在球，颈椎和腰骶区。她41岁的儿子有情绪抑郁和四肢感觉障碍的病史，同时伴有轻度肌肉萎缩、无力和反射减少。神经传导检查显示为中度感觉-运动多发性神经病，而脑部MRI正常。患者DNA的全外显子组测序鉴定出新的MFN2 （NM_014874.4）变体C . 581a >C p.（Asp194Ala）。结论：我们的研究结果为具有相同MFN2分子缺陷的家庭成员的异质临床表现提供了证据。此外，我们提出了第一例与MFN2突变相关的ASL-FTD病例，从而扩大了mfn相关疾病的范围。为了更好地了解MFN2在ALS-FTD发展中的作用，需要进一步的研究，包括更大的患者队列。
Background: MFN2 gene encodes the protein Mitofusin 2, involved in essential mitochondrial functions such as fusion, trafficking, turnover, and cellular interactions. We describe a family carrying a novel MFN2 mutation associated with ALS-frontotemporal dementia (FTD) clinical phenotype in the mother and Charcot-Marie-Tooth disease type 2A (CMT2A) in her son. Case presentation: The mother, a 67-year-old woman, referred to us for a three year-history of mood disturbance and gait impairment, and a more recent hypophonia, dysarthria, dysphagia, and diffuse muscle wasting. Family history was positive for psychiatric disorders and gait disturbances. Brain 18F-FDG PET showed severe hypometabolism in the fronto-temporal brain cortex bilaterally. Electrodiagnostic studies (EDX) showed severe motor axonopathy in the bulbar, cervical and lumbosacral districts. Her 41-year-old son had a history of mood depression and sensory disturbances in the limbs, along with mild muscle wasting, weakness, and reduced reflexes. Nerve conduction studies revealed a moderate sensory-motor polyneuropathy, while brain MRI was normal. Whole exome sequencing of the patients’ DNA identified the novel MFN2 (NM_014874.4) variant c.581A>C p.(Asp194Ala). Conclusion: Our findings provide evidence of heterogenous clinical manifestations in family members sharing the same MFN2 molecular defect. Additionally, we present the first documented case of ASL-FTD associated with an MFN2 mutation, thereby expanding the range of MFN-related disorders. Further research involving larger cohorts of patients will be needed to better understand the role of MFN2 as a contributing gene in the development of ALS-FTD.
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影响因子：
4.6
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
通讯作者：
Corti, Stefania
DOI：
10.3390/antiox6020025
发表时间：
2017-04-05
期刊：
Antioxidants (Basel, Switzerland)
影响因子：
--
作者：
Gao J;Wang L;Liu J;Xie F;Su B;Wang X
通讯作者：
Wang X
影响因子：
14.5
作者：
Burrell, James R.;Kiernan, Matthew C.;Hodges, John R.
通讯作者：
Hodges, John R.
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
影响因子：
4.8
作者：
Gaweda-Walerych K;Walerych D;Berdyński M;Buratti E;Zekanowski C
通讯作者：
Zekanowski C