LRP12基因5'非翻译区CGG异常重复扩增变异致眼咽远端型肌病四例  

Oculopharyngodistal myopathy caused by CGG repeat expansion in 5'untranslated region of LRP12 gene:four cases report

作　　者：于佳希 俞萌[1] 张巍[1] 袁云[1] 邓健文 王朝霞[1] YU Jia‑xi;YU Meng;ZHANG Wei;YUAN Yun;DENG Jian‑wen;WANG Zhao‑xia(Department of Neurology,Peking University First Hospital,Beijing 100034,China)

机构地区：[1]北京大学第一医院神经内科,100034

出　　处：《中国现代神经疾病杂志》2023年第9期798-806,共9页Chinese Journal of Contemporary Neurology and Neurosurgery

基　　金：国家自然科学基金资助项目(项目编号:82071409);国家自然科学基金资助项目(项目编号:U20A20356)。

摘　　要：目的回顾分析LRP12基因5’非翻译区(5’UTR)CGG异常重复扩增变异致眼咽远端型肌病(OPDM)1型患者临床经过,总结其临床和组织病理学特征。方法与结果纳入对象均为2008年1月至2023年8月在北京大学第一医院就诊并经基因检测确诊的OPDM1型患者,临床表现为以闭目无力、构音障碍、吞咽困难、面肌无力和四肢远端肌肉受累为主的肌无力特征,无眼球固定,其中2例伴上睑下垂;病程中血清肌酸激酶轻至中度升高(190~1211 U/L);3例患者下肢肌肉MRI呈不同程度脂肪化,以比目鱼肌和胫骨前肌受累明显。骨骼肌组织活检可见镶边空泡伴肌营养不良样改变;免疫荧光染色可见p62自噬蛋白和泛素蛋白阳性的核内包涵体形成。基因检测4例患者均携带LRP12基因5’UTR区CGG异常重复扩增变异,最终根据基因检测结果确诊为OPDM1型。结论OPDM1型患者多以双下肢远端无力和构音障碍发病,下肢肌肉受累不对称,肌肉以外组织器官较少受累,其临床表型和病理特征与其他眼咽远端型肌病亚型具有一致性。Objective To report the clinical and pathological features of 4 patients with oculopharyngodistal myopathy type 1(OPDM1)caused by CGG repeat expansion in the 5'untranslated region(5'UTR)of LRP12 gene.Methods and Results This study included 4 patients with OPDM1 who were admitted to Peking University First Hospital from January 2008 to August 2023.All 4 patients presented with weakness of eyes closed,dysarthria,dysphagia,facial muscle weakness and muscle weakness mainly involving distal muscles.None of 4 patients had restricted eye movements.Two of the patients had ptosis(Case 1 and Case 2).Serum creatine kinase(CK)levels were mildly to moderately elevated(190-1211 U/L)in 4 patients.Three patients(Case 1,Case 2 and Case 3)underwent lower extremity muscle MRI which showed varying degrees of fatty infiltration,with the soleus and tibialis anterior muscles being worst affected.Skeletal muscle biopsies in all 4 patients showed rimmed vacuoles with muscular dystrophy‑like pathological changes.Immunofluorescence staining revealed p62‑positive and ubiquitin‑positive intranuclear inclusions in all 4 patients.Genetic testing revealed that all 4 patients carried CGG repeat expansion in the 5'UTR of the LRP12 gene.Conclusions Most OPDM1 patients start with weakness in the distal extremities of both limbs and dysarthria.The involvement of muscles in the lower extremities is asymmetrical,and the involvement of tissues and organs other than muscles is not obvious.The remaining clinical phenotype and pathological features are consistent with other subtypes of OPDM.

关 键 词：神经肌肉疾病 三核苷酸重复扩增 病理学 

分 类 号：R746[医药卫生—神经病学与精神病学]