Del Bo R, Moggio M, Rango M, Bonato S, D'Angelo M G, Ghezzi S, Airoldi G, Bassi M T, Guglieri M, Napoli L, Lamperti C, Corti S, Federico A, Bresolin N, Comi G P
Dino Ferrari Centre, Department of Neurological Sciences, University of Milan, IRCCS Foundation Ospedale Maggiore Policlinico Mangiagalli and Regina Elena, Milan, Italy.
Neurology. 2008 Dec 9;71(24):1959-66. doi: 10.1212/01.wnl.0000327095.32005.a4. Epub 2008 Oct 22.
The axonal forms of Charcot-Marie-Tooth (CMT2) disease are a clinically and genetically heterogeneous group of disorders. Mitofusin 2 gene (MFN2) mutations are the most common cause of CMT2. Complex phenotypes have been described in association with MFN2 gene mutations, including CMT2 with pyramidal features (hereditary motor and sensory neuropathy [HSMN V]) and CMT2 with optic atrophy (HMSN VI).
To report on the clinical, neurophysiologic, and neuropathologic features of an Italian family with a novel MFN2 gene mutation and investigate brain functional parameters using magnetic resonance spectroscopy (MRS).
Three family members, a father and his two sons, were affected by peripheral neuropathy, cognitive impairment, and poor nocturnal vision (also optic neuropathy in one case). A member of this family also showed spastic paraparesis. The MFN2 gene sequence was analyzed. A sural nerve biopsy as well as brain (1)H-MRS and (31)P-MRS were evaluated in two patients.
Affected family members carried a novel MFN2 missense mutation, namely R104W, located within the critical GTPase domain of the protein which affects a highly conserved amino acid position. Sural nerve biopsies showed a normal mitochondrial network, particularly at the nodes of Ranvier, upon electron microscopy examination. A significant defect of high energy phosphates (HEPs) in the visual cortex was observed at rest by (31)P-MRS in the adult proband, while his son showed a defective recovery of HEPs after stimulation of the visual cortex.
Cognitive impairment may be another feature of the MFN2-related phenotype. The widespread peripheral and CNS involvement, as well as the neurosensorial defects, underline the similarities among MFN2-related and primary mitochondrial disorders.
夏科 - 马里 - 图斯病（CMT2）的轴索性形式是一组临床和遗传异质性疾病。线粒体融合蛋白2基因（MFN2）突变是CMT2最常见的病因。已描述了与MFN2基因突变相关的复杂表型，包括具有锥体特征的CMT2（遗传性运动和感觉神经病[HSMN V]）和伴有视神经萎缩的CMT2（HMSN VI）。
报告一个携带新型MFN2基因突变的意大利家族的临床、神经生理学和神经病理学特征，并使用磁共振波谱（MRS）研究脑功能参数。
三名家庭成员，一名父亲及其两个儿子，患有周围神经病变、认知障碍和夜间视力差（其中一例还患有视神经病变）。该家族的一名成员还表现出痉挛性截瘫。对MFN2基因序列进行了分析。对两名患者进行了腓肠神经活检以及脑氢质子磁共振波谱（1H - MRS）和磷磁共振波谱（31P - MRS）评估。
受影响的家庭成员携带一种新型的MFN2错义突变，即R104W，位于该蛋白关键的GTP酶结构域内，影响一个高度保守的氨基酸位置。电子显微镜检查显示腓肠神经活检中线粒体网络正常，尤其是在郎飞结处。成年先证者静息状态下通过31P - MRS观察到视觉皮层中高能磷酸盐（HEP）存在显著缺陷，而他的儿子在视觉皮层受到刺激后HEP恢复存在缺陷。
认知障碍可能是MFN2相关表型的另一个特征。广泛的外周和中枢神经系统受累以及神经感觉缺陷，突显了MFN2相关疾病和原发性线粒体疾病之间的相似性。
