Department of Neurosciences and Behavior Sciences, School of Medicine of Ribeirão Preto, University of São Paulo, USP, Brazil.
Neuromuscul Disord. 2011 Jun;21(6):428-32. doi: 10.1016/j.nmd.2011.03.008. Epub 2011 Apr 29.
Mutations of the mitofusin 2 (MFN2) gene have been reported to be the most common cause of the axonal form of Charcot-Marie-Tooth disease (CMT). The aim of this study was to describe a de novo MFN2 p.R104W mutation and characterize the associated phenotype. We screened the entire coding region of MFN2 gene and characterized its clinical phenotype, nerve conduction studies and sural nerve biopsy. Neuropsychological tests and brain MRI were also performed. A de novo mutation was found in exon 4 (c.310C>T; p.R104W). In addition to a severe and early onset axonal neuropathy, the patient presented learning problems, obesity, glucose intolerance, leukoencephalopathy, brain atrophy and evidence of myelin involvement and mitochondrial structural changes on sural nerve biopsy. These results suggest that MFN2 p.R104W mutation is as a hot-spot for MFN2 gene associated to a large and complex range of phenotypes.
已报道线粒体融合蛋白 2（MFN2）基因突变是轴索型腓骨肌萎缩症（CMT）最常见的原因。本研究旨在描述一种 MFN2 p.R104W 突变，并对其相关表型进行特征描述。我们筛查了 MFN2 基因的整个编码区，并对其临床表型、神经传导研究和腓肠神经活检进行了特征描述。还进行了神经心理学测试和脑 MRI。在第 4 外显子（c.310C>T；p.R104W）发现了一个新生突变。除了严重且早发性轴索性神经病外，该患者还表现出学习问题、肥胖、葡萄糖耐量异常、脑白质病、脑萎缩以及腓肠神经活检中髓鞘受累和线粒体结构改变的证据。这些结果表明，MFN2 p.R104W 突变是 MFN2 基因的热点突变，与广泛而复杂的表型相关。
