本文選題：脊髓小腦性共濟失調(diào)　切入點：基因　出處：《福建醫(yī)科大學》2014年碩士論文

【摘要】：目的：調(diào)查一脊髓小腦性共濟失調(diào)3型（spinocerebellar ataxia type3，SCA3）家系的遺傳譜系、臨床及電生理特征。方法：對福建地區(qū)一疑診為SCA3家系的11名家系成員進行基因檢測、影像學及神經(jīng)電生理檢查，并結(jié)合文獻分析SCA3的臨床及電生理特征。結(jié)果：1.在11名家系成員中，8名成員的基因檢測顯示CAG三核苷酸重復(fù)次數(shù)超出正常范圍：5名成員為現(xiàn)患者，CAG三核苷酸重復(fù)次數(shù)范圍為70～75次，平均（72.0±2.0）次，確診為SCA3；另3名成員雖無臨床癥狀，但CAG三核苷酸重復(fù)次數(shù)范圍為70～72次，平均（71.0±1.0）次，為未到發(fā)病年齡的SCA3癥狀前患者；其余3名成員CAG三核苷酸重復(fù)次數(shù)均在正常范圍。 2.家系4代22名成員中共有9例發(fā)病，每代均有患者，男女均受累，存在遺傳早現(xiàn)的現(xiàn)象�，F(xiàn)患者平均發(fā)病年齡為（41.0±2.9）歲，以進行性共濟失調(diào)為突出表現(xiàn)，如步態(tài)不穩(wěn)、動作笨拙（100%），且累及上、下運動神經(jīng)元：上運動神經(jīng)元受累主要表現(xiàn)為病理征陽性（100%）、腱反射活躍（80%）、肌張力增高（60%），下運動神經(jīng)元受累主要表現(xiàn)為肢體肌肉萎縮（80%）、肌無力（40%）。世界神經(jīng)病聯(lián)合會國際協(xié)作共濟失調(diào)評估量表(ICARS)評分在32～83分之間，臨床癥狀越嚴重，評分越高。 3.SCA3現(xiàn)患者顱腦MRI顯示小腦及腦干明顯萎縮，癥狀前患者顱腦MRI則無明顯異常。 4.SCA3存在體感神經(jīng)傳導(dǎo)通路、腦干聽覺傳導(dǎo)通路及視覺傳導(dǎo)通路的障礙，誘發(fā)電位提示該病具有中樞性及周圍性損害；體感誘發(fā)電位（SSEP）在疾病早期即可出現(xiàn)異常；神經(jīng)電圖檢查(NCSs)以感覺運動性軸索性損害為主，感覺纖維受累更為顯著，神經(jīng)傳導(dǎo)速度多在正常范圍；常規(guī)肌電圖（EMG）主要表現(xiàn)為神經(jīng)源性損害，并在肌肉萎縮明顯時可出現(xiàn)廣泛的纖顫波或束顫波等自發(fā)電位，與運動神經(jīng)元病(MND)的EMG類似。 結(jié)論：1.本家系經(jīng)研究證實，為SCA3合并運動神經(jīng)元受累（MNS）。 2.SCA3家系的外顯率高，患病者的CAG三核苷酸重復(fù)次數(shù)與正常人存在顯著差別，CAG三核苷酸重復(fù)次數(shù)檢測可為疾病的基因診斷及癥狀前診斷提供依據(jù)。 3.SCA3神經(jīng)電生理表現(xiàn)具有一定特征性：SCA3誘發(fā)電位提示中樞性及周圍性損害；SSEP可能是SCA3早期電生理改變的敏感指標，發(fā)現(xiàn)亞臨床損害；NCSs以感覺運動性軸索性損害為主；EMG主要表現(xiàn)為神經(jīng)源性損害。
[Abstract]:Objective: to investigate the genetic pedigree, clinical and electrophysiological characteristics of a family of spinocerebellar ataxia type 3 (SCA3) with cerebellar ataxia. Imaging and neuroelectrophysiological examination, The clinical and electrophysiological characteristics of SCA3 were analyzed in combination with literature. Results: 1.The gene tests of 8 out of 11 family members showed that the number of trinucleotide repeats of CAG exceeded the normal range of CAG trinucleotide repeats in 5 members of the family. The frequency ranges from 70 to 75, The mean number of CAG trinucleotide repeats was 72.0 鹵2.0 times and 71.0 鹵1.0 times respectively, and the other 3 members had no clinical symptoms, but the number of CAG trinucleotide repeats was 71.0 鹵1.0 times. The number of CAG trinucleotide repeats in the other 3 members were within normal range. 2. There were 9 cases of disease in 22 members of 4 generations in the family, each generation had patients, both men and women were involved, and there was an early occurrence of heredity. The average onset age of the present patient was 41.0 鹵2.9 years old, with progressive ataxia as a prominent manifestation, such as gait instability, The clumsy movements involved, Inferior motor neurons: the involvement of upper motor neurons is mainly manifested as pathological sign positive, tendon reflex is active, muscle tension is increased, muscle tension is increased, and inferior motor neurons are mainly manifested as limb muscle atrophy, myasthenia and myasthenia. The World Federation of Neuropathy. The ICARS score of the International Cooperative ataxia Assessment scale (ICARS) was between 32 and 83, The more severe the clinical symptoms, the higher the score. Craniocerebral MRI showed cerebellar and brainstem atrophy in present 3.SCA3 patients, but no significant abnormality in craniocerebral MRI in patients with 3.SCA3 before symptoms. In 4.SCA3, somatosensory nerve conduction pathway, brainstem auditory conduction pathway and visual conduction pathway were obstructed, and evoked potential showed central and peripheral damage, and somatosensory evoked potential (SSEP) was abnormal in the early stage of the disease. NCSs were mainly sensorimotor axonal damage, sensory fiber involvement was more significant, nerve conduction velocity was mostly in normal range, and routine electromyogram (EMG) showed neurogenic damage. A wide range of spontaneous potentials such as fibrillation wave or beam fibrillation wave can occur when muscle atrophy is obvious, which is similar to the EMG of motor neuron disease (MND). Conclusion [WT5HZ] [WT5BZ] [WT5 "HZ] [WT5BZ] [WT5" HZ] [WT5BZ] [WT5BZ]. The frequency of CAG trinucleotide repeats in 2.SCA3 families was significantly different from that in normal controls. The detection of 2.SCA3 trinucleotide repeats could provide evidence for gene diagnosis and pre-symptomatic diagnosis of the disease. The electrophysiological characteristics of 3.SCA3 suggested that central and peripheral lesions might be sensitive to early electrophysiological changes in SCA3. It was found that NCSs were mainly sensorimotor axonal damage and EMG was mainly neurogenic.
【學位授予單位】：福建醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2014
【分類號】：R744.7

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