肌细胞生成调节糖苷酶基因突变致原发性家族性脑钙化症一家系  

A family of primary familial brain calcification caused by myogenesis regulating glycosidase gene mutation

作　　者：刘瑛 曾一恒 姚香平 张安妮 吴旭玲 贺电 Liu Ying;Zeng Yiheng;Yao Xiangping;Zhang Anni;Wu Xuling;He Dian(Department of Neurology,the Affiliated Hospital of Guizhou Medical University,Guiyang 550001,China;Department of Neurology,the First Affiliated Hospital of Fujian Medical University,Fuzhou 350005,China)

机构地区：[1]贵州医科大学附属医院神经内科,贵阳550001 [2]福建医科大学附属第一医院神经内科,福州350005

出　　处：《中华神经科杂志》2021年第9期935-942,共8页Chinese Journal of Neurology

基　　金：国家自然科学基金培育项目(2020-2023,gyfynsfc[2020]-13)。

摘　　要：目的对原发性家族性脑钙化症(PFBC)一家系的临床特点和致病基因突变进行研究。方法收集2020年3月就诊于贵州医科大学附属医院的先证者及其家系成员的基本资料、临床特点和辅助检查结果。提取先证者外周血DNA,使用Sanger测序方法进行肌细胞生成调节糖苷酶(MYORG)基因突变的检测,同时对家系中部分成员采血,并采用同样检测方法对其进行先证者突变位点的验证。结果先证者为男性,30岁。该家系中仅有1例已发病的PFBC患者。先证者首发症状为言语含糊,逐渐出现动作变慢、行动灵活等锥体外系症状及高级认知功能损害。先证者与家系中1名无症状成员头颅CT均显示颅内多发对称性钙化灶,主要位于双侧小脑半球、基底节区及丘脑。二者MYORG基因第2号外显子的DNA序列均存在纯合突变位点c.1967T>C(p.I656T),而其余4名健康成员该位点亦检出杂合突变。结论MYORG基因纯合突变的患者均在CT扫描中发现钙化,病灶多位于基底神经节、小脑、皮质下白质及丘脑。与常染色体显性基因突变的患者相比,MYORG基因突变患者颅内钙化病灶更为广泛,并以脑桥-小脑病灶多见。MYORG基因突变的患者最常见的症状是运动障碍,以震颤麻痹及口齿不清多见。Objective To analyse the clinical presentation and pathogenic gene mutations of a family diagnosed with primary familial brain calcification(PFBC).Methods A pedigree with primary familial brain calcification was recruited.The clinical data of the proband who was admitted to the Affiliated Hospital of Guizhou Medical University in March 2020 and the family members were collected.The DNA sequence of myogenesis regulating glycosidase(MYORG)gene was detected by Sanger sequencing in the proband and some available family members.Results The proband is a male,30 years old.There was only one patient of PFBC in this family.The first symptom of the proband was vagueness of speech,and gradually extrapyramidal symptoms such as slow and flexible movement and advanced cognitive impairment appeared.The brain CT of the proband and his second brother showed extensive symmetrical calcifications,mainly located in the bilateral cerebellar hemispheres,basal ganglia and thalamus.A homozygous mutation in the exon 2 of the MYORG gene[c.1967T>C(p.I656T)]was identified in the proband and an asymptomatic patient.The heterozygous mutation of MYORG gene was also detected in four healthy family members.Conclusions All patients with homozygous mutations of MYORG gene showed calcification in CT scan,and most of the lesions were located in basal ganglia,cerebellum,subcortical white matter and thalamus.Compared with the patients with autosomal dominant gene mutation,the patients with MYORG gene mutation had more extensive intracranial calcification lesions,and the pontocerebellar lesions were more common.The most common symptoms of MYORG gene mutation patients were dyskinesia,mainly tremor paralysis and unclear speech.

关 键 词：钙质沉着症 脑 系谱 突变 MYORG基因 

分 类 号：R742[医药卫生—神经病学与精神病学]