常染色体显性遗传Emery—Dreifuss肌营养不良一家系研究并文献复习  

A family with autosomal dominant Emery-Dreifuss muscular dystrophy and literature review

作　　者：谈丹丹[1,2] 焦辉[1] 杨海坡[1] 常杏芝[1] 齐建光[1] 刘洁玉[1] 熊晖[1] 

机构地区：[1]北京大学第一医院儿科,100034 [2]南昌大学第一附属医院神经内科

出　　处：《中华实用儿科临床杂志》2013年第6期440-443,共4页Chinese Journal of Applied Clinical Pediatrics

基　　金：国家重点基础研究发展计划（2012CB944602）;北京市自然科学基金（7112133）

摘　　要：目的分析一个常染色体显性遗传Emery—Dreifuss肌营养不良（AD—EDMD）家系的临床、肌活检组织病理特征，探讨其致病基因突变。方法收集AD—EDMD家系先证者及其父母的临床资料，对先证者进行腓肠肌活检；提取先证者及其父母外周血基因组DNA，PCR扩增LMNA基因的12个外显子，以琼脂糖凝胶电泳鉴定PCR产物，PCR产物纯化后DNA直接测序，确定基因突变的类型，并综合文献进行分析。结果先证者，女，现4岁5个月，自幼四肢无力，以近端为著，轻度漏斗胸，肌酶水平升高，肌电图提示肌源性损害，腓肠肌活检病理学检查提示肌肉病样改变。其父亲具有相同症状，随病程进展表现为早期出现肘关节挛缩，颈部僵硬，脊柱侧弯，跟腱紧，四肢缓慢进行性肌无力，窦性心动过缓等。LMNA基因突变分析发现先证者及其父亲LMNA基因第9外显子发生杂合错义突变C．1580G〉C（P．Arg527Pro），此为已报道致病突变。结论对早期出现肘关节挛缩、屈颈受限、脊柱强直、双上肢近端和双下肢远端肌无力明显、心律失常的患者应分析LMNA基因，有助于早期诊断EDMD，判断预后；及时有效监测心律失常的变化，适时干预，从而改善生活质量，延长寿命。基因分析是确诊EDMD最可靠的方法。Objective To analyze the clinical characteristics,muscle pathological features and pathogenic gene mutation of a family with autosomal dominant Emery-Dreifuss muscular dystrophy （AD-EDMD）. Methods Clinical data of the proband and her family members, a Chinese family of AD-EDMD, were collected. Skeletal muscle speci- mens were collected from the proband for pathological analysis. Genomie DNA from the proband and her parents was ex- tracted using standard procedures from the peripheral blood leukocytes. PCR and DNA direct sequencing were employed to analyze all of the 12 exons of the LMNA gene to determine the gene mutation, and the case was summarized along with related literature review. Results The proband, female, 4 years and 5 months old now, presented with muscle weakness during her early childhood, the proximally was more prominent, mild peetus excavatum. Her CK level was ele- vated, her electromyogram showed myogenic injuries, the muscle biopsy showed myopathy changes. Her father had the same symptom, with disease progressed, showed elbow contractures in early stage, stiff neck, tight achilles tendon, slowly progressive muscle weakness of the limbs, sinus bradycardia. A heterozygous missense mutation c. 1580G 〉 C （ p. Arg527Pro） was identified in exon 9 of the LMNA gene in the proband and her father,but not in her mother. This hete- rozygous missense mutation had been reported as a pathogenic gene mutation. Conclusions The patient who has elbow contraetures in early stage, limited neck flexion, spine stiffness, muscle weakness with the proximal upper limbs and dis- tal lower limbs,and arrhythmia,should have an analysis of the LMNA gene. It＇s important for the early diagnosis of ED- MD ,assessment of the prognosis ,timely and effectively monitoring the changes of arrhythmia, then taking interventions to improve the quality of life and prolong life. So genetic analysis is most reliable method to diagnose EDMD.

关 键 词：Emery—Dreifuss肌营养不良 LMNA基因 突变 关节挛缩 

分 类 号：R74[医药卫生—神经病学与精神病学]