Mutated mitofusin 2 presents with intrafamilial variability and brain mitochondrial dysfunction

作者：Roberto Del Bo, Maurizio Gualtiero Moggio, Mario Rango, S. Bonato, Maria Grazia D’Angelo, Serena Ghezzi, Giovanni Airoldi, Maria Teresa Bassi, Michela Guglieri, Laura Napoli, Costanza Lamperti, Stefania Paola Corti, Antonio Federico, Nereo Bresolin, Giacomo P. Comi · 发表于：Neurology · 年份：2008 · DOI：10.1212/01.wnl.0000327095.32005.a4 · 被引用次数：94 · 研究领域：Hereditary Neurological Disorders、Genetic Neurodegenerative Diseases、Mitochondrial Function and Pathology

BACKGROUND: 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). OBJECTIVE: 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). METHODS: 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. RESULTS: 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 def...