摘要
目的报道常染色体隐性遗传痉挛性共济失调(ARSACS)家系1病例,对亚裔人群ARSACS的临床特征和基因变异进行分析。方法回顾ARSACS患者临床资料,采用全外显子测序方法对收治的ARSACS家系1病例进行基因检测。结合文献报道的16个亚裔ARSACS家系资料进行对比分析。结果ARSACS病例典型临床表现为小脑共济失调合并痉挛及周围神经病变。先证者携带S4CS基因上纯合无义突变(c.11374C>T,p.R3792X),未患病的父母携带该位点的单杂合突变。先证者姐姐通过一代测序验证亦携带上述纯合突变。先证者及先证者姐姐儿童时期有着同样的症状:剪刀步态和宽基步态、眼震、手足畸形,肌电图及神经传导速度提示感觉运动性周围神经病、头颅MRI显示小脑萎缩。先证者姐姐尚有双侧肺大泡。结论ARSACS的基因突变类型及位点各异,由编码sacsin蛋白的SACS基因突变引起的神经退行性疾病,ARSACS在亚洲人群中罕见,无特定的高频突变。诊断主要依靠临床症状体征及辅助检查如肌电图等,不典型患者,基因筛查至关重要。
Aim To report one autosomal recessive spastic ataxia of Charlevoix-Saguenay(ARSACS)family,and analyze the clinical features and gene variants in Asian population.Methods The clinical data was reviewed,and the whole exome sequencing on the patient was performed.Sixteen Asian ARSACS pedigrees were reviewed and analyzed.Results ARSACS was characterized by early-onset cerebellar ataxia with spasticity and peripheral neuropathy.The proband carried the homozygous pathogenic nonsense mutations(c.11374C>T,p.R3792X)in SACS,while the unaffected parents carried the single heterozygous mutation.His sister was proved by Sanger sequencing to carry the homozygous mutations.Two patients had similar symptoms in their childhood:scissors gait and wide base gait,nystagmus,limb ataxia,finger and foot deformities,sensorimotor peripheral neuropathy on electromyography and nerve conduction velocity,and cerebellar atrophy on MRI.His sister also had bilateral bullae of lung.Conclusion ARSACS,with a variant type and location of gene mutations,is a neurodegenerative disorder resulted from mutation in sacsin-coding gene SACS.It was seldom reported in Asian population and without hotspot mutations.The diagnosis depends on clinical manifestation and examination such as electromyography.For atypical patients,genetic testing was important.
作者
关荣源
孙一忞
孙高园
王坚
邬剑军
GUAN Rong-yuan;SUN Yimin;SUN Gao-yuan;WANG Jian;WU Jian-jun(Department of Neurology,National Clinical Research Center for Aging and Medicine,Huashan Hospital,Fudan University,Shanghai 200040,China;Department of Neurology,Shanghai Jing 5 an District Center Hospital,Fudan University,Shanghai 200040,China;Hankou Aier Eye Hospital,Wuhan 430000,China)
出处
《中国临床神经科学》
2019年第6期644-651,共8页
Chinese Journal of Clinical Neurosciences
