Calvo Judith, Funalot Benoît, Ouvrier Robert A, Lazaro Leila, Toutain Annick, De Mas Philippe, Bouche Pierre, Gilbert-Dussardier Brigitte, Arne-Bes Marie-Christine, Carrière Jean-Pierre, Journel Hubert, Minot-Myhie Marie-Christine, Guillou Claire, Ghorab Karima, Magy Laurent, Sturtz Franck, Vallat Jean-Michel, Magdelaine Corinne
Service de neurologie, Centre Hospitalier Universitaire (CHU) de Limoges, Limoges, France.
Arch Neurol. 2009 Dec;66(12):1511-6. doi: 10.1001/archneurol.2009.284.
Mutations in the gene encoding mitofusin 2 (MFN2) cause Charcot-Marie-Tooth disease type 2 (CMT2), with heterogeneity concerning severity and associated clinical features.
To describe MFN2 mutations and associated phenotypes in patients with hereditary motor and sensory neuropathy (HMSN).
Direct sequencing of the MFN2 gene and clinical investigations of patients with MFN2 mutations.
Molecular genetics laboratory of a university hospital and the Limoges National Referral Center for Rare Peripheral Neuropathies.
One hundred fifty index patients with HMSN and a median motor nerve conduction velocity of 25 m/s or greater and without mutations in the genes encoding connexin 32 and myelin protein zero.
Results of genetic analyses and phenotypic observations.
Twenty different missense mutations were identified in 20 index patients. Mutation frequency was 19 of 107 (17.8%) in patients with CMT2 and 1 of 43 (2.3%) in patients with a median motor nerve conduction velocity less than 38 m/s. Four patients had proven de novo mutations, 8 families had autosomal dominant inheritance, and 3 had autosomal recessive inheritance. The remaining 5 patients were sporadic cases with heterozygous mutations. Phenotypes varied from mild forms to early-onset severe forms. Additional features were encountered in 8 patients (32%). Six patients underwent sural nerve biopsy: electronic microscopy showed prominent mitochondrial abnormalities on longitudinal sections.
MFN2 mutations are a frequent cause of CMT2, with variable severity and either dominant or recessive inheritance. MFN2 gene testing must be a first-line analysis in axonal HMSN irrespective of the mode of inheritance or the severity of the peripheral neuropathy.
编码线粒体融合蛋白2（MFN2）的基因突变会导致2型遗传性运动感觉神经病（CMT2），其严重程度和相关临床特征存在异质性。
描述遗传性运动感觉神经病（HMSN）患者的MFN2突变及相关表型。
对MFN2基因进行直接测序，并对MFN2突变患者进行临床研究。
大学医院分子遗传学实验室和利摩日国家罕见周围神经病转诊中心。
150例HMSN索引患者，正中运动神经传导速度为25米/秒或更高，且编码连接蛋白32和髓鞘蛋白零的基因无突变。
基因分析结果和表型观察。
在20例索引患者中鉴定出20种不同的错义突变。CMT2患者的突变频率为107例中的19例（17.8%），正中运动神经传导速度小于38米/秒的患者中为43例中的1例（2.3%）。4例患者有证实的新发突变，8个家系为常染色体显性遗传，3个家系为常染色体隐性遗传。其余5例患者为杂合突变的散发病例。表型从轻度到早发型重度不等。8例患者（32%）出现其他特征。6例患者进行了腓肠神经活检：电子显微镜检查显示纵切面上线粒体异常明显。
MFN2突变是CMT2的常见病因，严重程度各异，遗传方式为显性或隐性。无论遗传方式或周围神经病的严重程度如何，MFN2基因检测都必须作为轴索性HMSN的一线分析方法。
