摘要 目的总结常染色体显性遗传性DNAJB6基因突变所致肌病的临床表型和基因突变特点。方法回顾分析一家系2例DNAJB6基因突变所致肌病患者的临床表现、实验室、肌肉影像学、神经电生理学、肌肉病理学和基因检测结果,并进行文献复习。结果先证者主要表现为四肢远近端肌无力,下肢重于上肢、近端重于远端,其父呈姿势异常,上楼需扶持。二者血清肌酸激酶水平正常,MRI表现为不同程度肌肉脂肪化,组织病理学可见肌营养不良样改变,部分肌纤维内镶边空泡形成,核内移增多或个别肌纤维再生。基因检测提示先证者及其父均携带DNAJB6基因c.161A>C(p.Glu54Ala)杂合突变,为中国大陆首次报道,分别为肢带型肌营养不良症D1型(LGMD⁃D1型)和远端型肌病型,该家系明确为常染色体显性遗传性DNAJB6基因突变所致肌病家系。结合文献提示DNAJB6基因突变所致肌病临床表现存在异质性,同一家系可表现为不同的临床亚型。结论DNAJB6基因突变可导致肢带型肌营养不良症和远端型肌病两种表型,肌肉病理均呈现镶边空泡和肌营养不良样改变。该家系进一步扩展了DNAJB6基因突变的表型谱。 Objective To summarize the clinical phenotypes and genetic mutations of DNAJB6 related myopathies.Methods We retrospectively reviewed the clinical information,laboratory tests,muscle MRIs,electromyography results,muscle pathology examinations and genetic mutations of 2 patients of DNAJB6 related myopathies from one family and reviewed related published literatures of DNAJB6 related myopathies.Results The proband presented with muscle weakness of both proximal and distal limbs,with lower limbs more serious than upper limbs,and proximal more serious than distal.The father of proband presented with abnormal gait,and he could only climb stairs with assistance.Serum creatine kinase(CK)levels of both patients were normal.Muscle MRIs of both patients showed different degrees of fatty infiltration.Muscle biopsies of both patients showed similar changes with dystrophic features,and some muscle fibers with rimmed vacuoles inside,as well as increased internal nuclei and a few regenerating fibers.Genetic tests proved both patients carried the same DNAJB6 gene variant,c.161A>C(p.Glu54Ala),which was the first report in mainland China.The proband was diagnosed as limb⁃girdle muscular dystrophy D1(LGMD⁃D1)type,and the father of proband was diagnosed as distal myopathy.This family was considered as autosomal dominant DNAJB6 related myopathy.Referring to literature,heterogeneities exist in DNAJB6 related myopathies,and different clinical phenotypes could be presented in one single family.Conclusions The phenotypes of DNAJB6 related myopathies include limb⁃girdle muscular dystrophy and distal myopathy.Muscle pathology shows similar changes of rimmed vacuoles and dystrophic features.This reported family further expands the spectrum of phenotypes of DNAJB6 related myopathies.
机构地区 北京大学第一医院神经内科
出处 《中国现代神经疾病杂志》 CAS 北大核心 2021年第3期204-211,共8页 Chinese Journal of Contemporary Neurology and Neurosurgery
关键词 肌疾病 肌营养不良 肢带型 远端型肌营养不良症 基因 突变 系谱 Muscular diseases Muscular dystrophies,limb⁃girdle Distal myopathies Genes Mutation Pedigree
分类号 R73 [医药卫生—肿瘤]
