CAJ | 학술논문

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。
목적 보도1개유전성운동감각성신경병6형가계적림상표현、병리개변이급기인돌변특점。방법 선증자남성，15세。환자5세출현쌍하지무력，증상진행성가중，반수출현쌍족근건련축；11세개시출현만성진행성시력하강；12세출현쌍수기육위축，무지체마목。주위신경전도속도검사현시유발전위미능인출혹파폭현저하강，감각신경교운동신경개변경명현。시유발전위제시쌍안P100잠복기균연장，파폭정상。안저조상제시시신경위축，시망막전도정상。환자모친7세시개시출현주로비력，10세출현시력하강。대선증자진행비장신경활체조직검사。대선증자급기모친진행선립체융합단백2( MFN2)기인측서，100명건강인작위정상대조。결과 비장신경병리개변주요위유수신경섬유현저감소，전경검사발현개별유수신경섬유출현양총구양결구화재생족결구，개별신경섬유적축색내가견선립체취집화공포화。선증자화모친적MFN2기인제19호외현자존재c.2218T＞C잡합돌변，도치MFN2제740위적색안산유정안산체대(W740R)。100명건강대조몰유발현해돌변。결론 MFN2기인c.2218T＞C돌변도치료유전성운동감각성신경병6형，기시력하강다출현재척신경손해지후，주위신경가이존재수초손해。
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.