眼咽型肌营养不良二家系的临床、影像学特点及致病基因分析

Clinical,imaging and genetic analyses of two Chinese families with oculopharyngeal muscular dystrophy

目的介绍2个眼咽型肌营养不良(OPMD)家系的临床、影像学及致病基因特点。方法安阳市人民医院神经内科2016年8月、2018年5月发现2个OPMD家系,对其全部成员展开详细调查,并对先证者临床及影像学资料进行分析;采集22名成员的外周静脉血进行PABPN1基因分析。结果家系1成员4代,患者共4例;家系2成员3代,患者共4例。2例先证者分别于50岁、55岁以后出现双眼睑下垂、吞咽困难;家系1先证者伴复视、肌肉萎缩及四肢无力,肌电图提示神经源性改变,肌肉病理可见镶边空泡样变肌纤维,胸部CT提示吸入性肺炎,头颅MRI可见脑干对称性白质病变;家系2先证者伴眼肌麻痹及偏侧肢体无力,无复视及肌肉萎缩,肌电图提示肌源性改变,胸部CT正常,头颅MRI提示双侧顶叶、右侧额叶腔隙性梗死。PABPN1基因分析发现2家系被检测患者PABPN1基因三核苷酸(GCN)重复突变,由正常的(GCG)6(GCA)3(GCG)扩增为(GCG)6(GCA)3(GCG)2(GCA)3(GCG)。结论OPMD具有临床异质性,头颅MRI可出现脑干对称性白质病变。国内OPMD患者存在PABPN1基因突变,具体表现为(GCG)6(GCA)3(GCG)2(GCA)3(GCG)重复突变。

Objective To study the clinical,imaging and genetic characteristics of two Chinese families with oculopharyngeal muscular dystrophy(OPMD).Methods The clinical data of the two families found in our hospital in August 2016 and May 2018 were analyzed.All the members were investigated in detail,and the clinical and imaging data of the probands were analyzed.Blood samples were collected from 22 members of the two families and PABPN1 gene analysis was performed.Results There were 4 patients in family 1 with four generations and 4 patients in family 2 with three generations.The two probands presented ptosis,dysphagia at the age of 50 and 55.The proband of family 1 also showed diplopia,amyotrophy,weakness of proximal limbs,neurogenic changes in electromyogram(EMG),muscle fibers with rimmed vacuoles in muscle pathology,aspiration pneumonia in chest CT,and brainstem symmetric white matter lesions in cranial MR imaging.The proband of family 2 also showed eye muscle paralysis and lateral limb weakness,myogenic changes in EMG,bilateral parietal and right frontal lacunar infarctions in cranial MR imaging.Analysis of PABPN1 gene showed that the repeated mutation of PABPN1 trinucleotide(GCN)in 2 families was amplified from normal(GCG)6(GCA)3(GCG)to(GCG)6(GCA)3(GCG)2(GCA)3(GCG).Conclusion OPMD has clinical heterogenicity;symmetrical white matter lesions in the brainstem might be found in cranial MR imaging;Chinese patients with OPMD have PABPN1 gene mutation,specificly manifested as(GCG)6(GCA)3(GCG)2(GCA)3(GCG)repeat mutations.