新发复合杂合突变导致迟发型常染色体隐性遗传性痉挛性共济失调Charlevoix-Saguenay型  

Novel spastic ataxia of Charlevoix-Saguenay gene compound heterozygous mutations in late onset autosomal recessive spastic ataxia of Charlevoix-Saguenay

作　　者：孙葳[1] 俞萌[1] 卓勇杰 王朝霞[1] 袁云[1] 

机构地区：[1]北京大学第一医院神经内科,100034 [2]山西省襄汾县人民医院神经内科

出　　处：《中华神经科杂志》2017年第11期831-836,共6页Chinese Journal of Neurology

基　　金：科技部“十二五”重大专项课题（2011ZX09307-001-07）

摘　　要：目的 探讨1例SACS（spastic ataxia of Charlevoix-Saguenay）基因新发复合杂合突变导致的迟发型常染色体隐性遗传性痉挛性共济失调Charlevoix-Saguenay型（autosomal recessive spastic ataxia of Charlevoix-Saguenay,ARSACS）患者的临床和实验室检查特点.方法 患者为26岁汉族男性,13岁发病,表现为双下肢力弱、发僵、行走不稳,体检示双下肢锥体束征、小脑性共济失调和感觉运动性周围神经病,并有手指关节弹性过度、手指天鹅颈样畸形、高弓足和锤状趾.对患者进行眼底照相和光学相干成像、头和颈椎MRI、周围神经传导速度、运动诱发电位、视觉和脑干听觉诱发电位、周围神经超声、大腿MRI、眼震电图和基因靶向二代测序等检查并分析结果.结果 患者眼底照相和光学相干成像示双侧视盘边界不清、视网膜神经纤维层增厚.其头颅磁共振T2 WI和T2 FLAIR示双侧脑桥对称性条纹状低信号,脑桥小脑脚增粗,颈髓和上胸髓萎缩变细.神经电生理示周围感觉神经传导未引出,运动神经传导速度减慢,复合肌肉动作电位波幅在上肢所检神经未见异常,在下肢所检神经下降82%~100%.运动诱发电位中枢传导时间延长.基因靶向二代测序并经Sanger测序验证发现SACS基因存在新发复合杂合突变,分别为c.12637_12638delGA（p.Glu4213ArgFs＊3）和c.11274_11276delAAC（p.Ile3758_Thr3759delinsMet）,经家系验证该突变分别来自患者母亲和父亲.结论 认识ARSACS三联征、眼底和头磁共振表现有助于临床诊断.该例患者扩大了ARSACS的临床和遗传谱.Objective To investigate the clinical features and laboratory results in a patient with late onset autosomal recessive spastic ataxia of Charlevoix-Saguenay （ ARSACS ） carrying novel SACS （ spastic ataxia of Charlevoix-Saguenay ） gene heterozygous mutations .Methods A 26-year-old Chinese man developed since the age of 13 a progressive weakness and stiffness of his bilateral lower limbs and gait unsteadiness.He had pyramidal tract sign in his bilateral lower limbs , cerebellar ataxia and sensory-motor polyneuropathy , with hyperelastica and swan neck-like deformities of the fingers , pes cavus and hammer toes.Funduscopy and optical coherence tomography , brain and cervical MRI , conduction velocity of peripheral nerve , motor evoked potentials , visual and brainstem auditory evoked potentials , ultrasound of peripheral nerve , hips and legs MRI , electronystagmography , and targeted capture and next generation sequencing were performed .Results Funduscopy and optical coherence tomography revealed thickening of the retinal nerve fiber layer with unclear margined optic disc .MRI revealed symmetrical linear hypointensity lesions in the pons on T 2 and T2 FLAIR weighted images , thickened bilateral cerebellar peduncles , and flattened and atrophied cervical and upper thoracic spinal cord .Nerve conduction studies showed sensory nerve action potentials were absent in four limbs , motor conduction velocity was slowed , amplitude of muscle response was significantly decreased in lower-limb nerves （ decreased by 80% -100%） but normal in upper-limb nerves.Central motor conduction time of motor evoked potential was prolonged .Targeted capture and next generation sequencing revealed novel SACS compound heterozygous mutations , c.12637 _12638delGA （p.Glu4213ArgFs＊3） and c.11274_11276delAAC （p.Ile3758_Thr3759delinsMet） derived from each parent respectively , which were confirmed by Sanger sequencing analyses . Conclusions Recognizing ARSACS triad and its characteristics on fundus and brain MRI is helpful

关 键 词：脊髓小脑变性 共济失调 多发性神经病 磁共振成像 突变 

分 类 号：R744.7[医药卫生—神经病学与精神病学]