线粒体融合蛋白2基因新突变导致的遗传性运动感觉性神经病6型一家系

目的 报道1个遗传性运动感觉性神经病6型家系的临床表现、病理改变以及基因突变特点。方法 先证者男性，15岁。患者5岁出现双下肢无力，症状进行性加重，伴随出现双足跟腱挛缩；11岁开始出现慢性进行性视力下降；12岁出现双手肌肉萎缩，无肢体麻木。周围神经传导速度检查显示诱发电位未能引出或波幅显著下降，感觉神经较运动神经改变更明显。视诱发电位提示双眼P100潜伏期均延长，波幅正常。眼底照相提示视神经萎缩，视网膜电图正常。患者母亲7岁时开始出现走路费力，10岁出现视力下降。对先证者进行腓肠神经活体组织检查。对先证者及其母亲进行线粒体融合蛋白2( MFN2)基因测序，100名健康人作为正常对照。结果 腓肠神经病理改变主要为有髓神经纤维显著减少，电镜检查发现个别有髓神经纤维出现洋葱球样结构和再生簇结构，个别神经纤维的轴索内可见线粒体聚集和空泡化。先证者和母亲的MFN2基因第19号外显子存在c.2218T＞C杂合突变，导致MFN2第740位的色氨酸由精氨酸替代(W740R)。100名健康对照没有发现该突变。结论 MFN2基因c.2218T＞C突变导致了遗传性运动感觉性神经病6型，其视力下降多出现在脊神经损害之后，周围神经可以存在髓鞘损害。

A new MFN2 gene mutation resulting in hereditary motor and sensory neuropathy type 6, a family report

Objective To report clinical, pathological and molecular genetic features in a Chinese family with hereditary motor and sensory neuropathy type 6. Methods The index case is a 15 years old boy. He developed progressive distal limb weakness at the age of 5. The disease deteriorated slowly,accompanied with contracture of achilles' tendon. At the age of 11 years old he suffered from decrease of visual acuity. At the age of 12, he found the muscular atrophy of both hands without sensory disturbances.Visual evoked potential revealed prolonged latency of bilateral P100. Ophthalmological examination showed bilateral optic atrophy. His mother had the similar symptoms at the age of 7 and reduced visual acuity at the age of 10. Nerve conduction velocity revealed in both pat1ents no compound motor and sensory nerve action potentials in most nerves or slightly reduced nerve conduction velocities with severely reduced amplitudes of the compound motor and sensory nerve action potentials. Sural nerve biopsy was performed on the proband.The sequence of MFN2 gene was analyzed in DNA from the index, his mother and 100 healthy controls.ResultsSural nerve biopsy revealed severe loss of myelinated fibers with few regenerating clusters.Ultrapathological examination showed a few of atypical bulbs of myelinated fibers, occasionally regenerating clusters, mitochondrial swelling and aggregation in a few of axons. A new mutation of W740R mutation in MFN2 gene has been identified in the index case, her mother, but not in 50 healthy controls. Conclusions A novel MFN2 gene mutation result in hereditary motor and sensory neuropathy type 6. Mild visual loss appeares after the lesion of spinal nerves. Demyelination of peripheral nerve appears in the disease.