伴镶边空泡远端肌病的临床、病理及GNE基因突变分析

发布时间：2018-03-17 12:20

本文选题：伴镶边空泡远端肌病(DMRV)　切入点：唾液酸　出处：《吉林大学》2017年硕士论文　论文类型：学位论文

【摘要】：目的:回顾性分析我院收治的7例DMRV患者的临床、病理及影像学检查,并进一步分析其基因突变特点,结合世界范围内本病的突变热点报道,了解我国基因突变谱,增加临床医师对该病的认识。材料和方法:7例患者均于2013至2016年间就诊于吉林大学第一医院神经内科并诊断为DMRV。收集患者临床资料,进行肌酸激酶、肌肉组织活检、肌电图及肌肉MRI检查,取患者外周血进行基因检测。结果:1、临床特点:7例患者就诊时年龄为26-46岁,平均起病年龄29.8岁,病程2-10年不等,2例男性,5例女性。其中以双下肢无力起病4例,双上肢无力起病1例,四肢无力起病2例。7例患者均以远端肢体无力为主,下肢胫骨前肌受累明显,肌萎缩以小腿及手部肌群萎缩多见,4例患者伴有足下垂及“鸭步”,股四头肌均不受累,腱反射多减弱或消失。2、辅助检查:4例CK轻度至中度升高,不超过3倍,肌电图均为肌源性损害。对其中3例进行肌肉MRI检查,提示双小腿以胫骨前肌、胫骨后肌、趾长伸肌、腓骨长肌、腓骨短肌、腓肠肌受累为主,双大腿以内侧群及后群肌肉受累为主。肌肉MRI主要表现为肌肉萎缩及脂肪变性,股四头肌均不受累,未见明显炎症性渗出。3、肌肉病理特点:7例患者均行开放式肌肉组织活检。患者肌肉病理苏木素-伊红(hematoxylin-eosin,H-E)染色均可见镶边空泡及其内嗜碱性颗粒沉积,肌纤维大小不等,改良Gomori三原色(Modified Gomori trichrome,MGT)染色在细胞质的空泡边缘可见红色颗粒,均未见炎细胞浸润,可见变性、坏死肌纤维。4、基因突变特点:共发现8个基因突变位点,1例移码突变,其余均为错义突变,其中,5个为已知的致病性突变:p.D207V、p.C44S、p.G576R、p.A669P、p.D218G,3个为未知突变:c.455_456ins C、p.P421L、p.A287T。结论:本组7例患者均为散发,没有家族史,均成年早期发病,首发症状多为双下肢远端无力或步态异常,胫骨前肌受累明显,病情缓慢进行性加重,CK轻度或中度升高,肌肉活检病理证实存在典型镶边空泡,肌纤维大小不等,未见炎细胞浸润。对其中3名患者进行肌肉MRI检查提示小腿肌群及大腿内侧、后侧肌群肌萎缩及脂肪变性明显,股四头肌相对不受累,故7例患者均符合DMRV的临床病理诊断。进一步对患者外周血行基因检测分析,均发现GNE基因突变,因此,DMRV诊断明确。7例患者基因检测结果发现有已知致病性突变及未知突变,丰富了我国的GNE基因突变谱。
[Abstract]:Objective: to retrospectively analyze the clinical, pathological and imaging findings of 7 patients with DMRV in our hospital, and further analyze the characteristics of gene mutation. Materials and methods from 2013 to 2016, 7 patients were admitted to Department of Neurology, first Hospital of Jilin University and diagnosed as DMRV.Clinical data were collected, creatine kinase and muscle tissue biopsy were performed. Results: the clinical features of 7 patients were 26 to 46 years old, with an average onset age of 29.8 years. The course of disease ranged from 2 to 10 years in 2 cases of male and 5 cases of female, including 4 cases of bilateral lower extremity weakness, 1 case of double upper limb weakness, and 7 cases of limb weakness. Muscle atrophy of the calf and hand was more common in 4 patients with foot droop and "duck step", quadriceps femoris were not involved, tendon reflex was weakened or disappeared .2. minor to moderate elevation of CK was found in 4 cases of assist examination, which was not more than 3 times. Electromyogram (EMG) was found to be myogenic damage in 3 cases. The results showed that the anterior tibial muscle, posterior tibial muscle, extensor digitorum longus muscle, fibula longus muscle, brevis fibula muscle and gastrocnemius muscle were involved in the three cases. The medial group and posterior group of muscles were mainly involved in both thighs. Muscle MRI was mainly characterized by muscular atrophy and fatty degeneration, and quadriceps femoris were not involved. There was no obvious inflammatory exudation. The muscle pathological features of 7 patients were all performed open muscle tissue biopsy. The myopathological hematoxylin-eosinine H-E staining of all the patients showed edging vacuoles and their basophilic granules deposition, and the size of muscle fibers varied. Modified Gomori tricolor Gomori trichrome MGTstaining showed red particles on the edge of vacuole of cytoplasm, no inflammatory cell infiltration, degeneration, necrotic muscle fiber .4. gene mutation characteristics: one case of frameshift mutation was found at 8 gene mutation sites. The others were missense mutations, of which 5 were known pathogenicity mutations: 1 / p.D207V / p. C44SU p. G576R / p. A669P / D218G, 3 unknown mutation: c.455456ins Cnp. P421L / A287T.Conclusion: all of the 7 patients were sporadic, had no family history, and all had early onset of adulthood. Most of the initial symptoms were weakness or gait abnormality of distal lower extremity, obvious involvement of anterior tibial muscle, mild or moderate elevation of CK slowly and progressively aggravated, typical edge vacuole was confirmed by muscle biopsy, and the size of muscle fiber varied. No inflammatory cell infiltration was found. MRI examination of the muscles of 3 of them showed that the muscle group of the leg and the medial thigh, the atrophy and fatty degeneration of the posterior muscle group were obvious, and the quadriceps femoris muscle was relatively unaffected. Therefore, all the 7 patients were in accordance with the clinicopathological diagnosis of DMRV. Further analysis of GNE gene in peripheral blood showed that the mutation of GNE gene was found in all patients. Therefore, the gene detection results of 7 patients confirmed that there were known pathogenicity mutations and unknown mutations. It enriches the GNE gene mutation profile in China.
【学位授予单位】：吉林大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R746

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