中国SPG11患者的临床与分子遗传学研究  

Research on clinical and molecular genetics of hereditary spastic paraplegia 11 patients in China

作　　者：杜鹃[1] DU Juan(Department of Neurology,Xiangya Hospital,Central South University,Changsha 410078,China)

机构地区：[1]中南大学湘雅医院神经内科,长沙410078

出　　处：《中南大学学报（医学版）》2022年第12期1729-1732,共4页Journal of Central South University ：Medical Science

基　　金：国家自然科学基金(81100845)。

摘　　要：遗传性痉挛性截瘫(hereditary spastic paraplegia,HSP)是一类主要由皮质脊髓束受损引起的罕见的神经系统遗传性疾病。HSP遗传方式多样,可以呈常染色体显性遗传、常染色体隐性遗传、X连锁遗传,某些病例呈线粒体遗传。目前HSP至少分为80余种亚型,SPG11是常染色体隐性遗传HSP中最常见的亚型,其致病基因为KIAA1840,编码spatacsin蛋白。国内已发现有52例SPG11患者,发病年龄4~24岁。其首发症状为走路不稳和/或智力障碍,临床表现包括智力障碍、括约肌功能障碍、视力下降、共济失调、弓形足、肌萎缩、眼肌麻痹及周围神经病等。除胼胝体变薄及脑室周围白质改变外,患者还可表现为大脑皮质萎缩、小脑萎缩、脑室扩大等。中国SPG11患者具有明显的临床及遗传异质性,其发病率并无明显的性别差异。在中国SPG11患者中共检测出KIAA1840基因致病突变37个,均可导致spatacsin蛋白截短突变,其中KIAA1840基因移码突变是最常见的突变类型。The hereditary spastic paraplegia(HSP)is a rare hereditary disease in nervous system due to the damage of corticospinal tract.HSP has various inheritance modes,including autosomal dominant inheritance,autosomal recessive inheritance,X-linked inheritance,and mitochondrial inheritance in some cases.At present,there are at least 80 subtypes of HSP.Hereditary spastic paraplegia type 11(SPG11)is the most common subtype in autosomal recessive inheritance,and its pathogenic factor is KIAA1840 gene,which encodes spatacsin protein.A total of 52 SPG11 patients aged from 4−24 years old have been reported.Their initial symptoms were gait disturbance and/or mental retardation.As the disease develops,they may present with mental retardation,sphincter disturbance,decreased vision,ataxia,amyotrophy,pes arcuatus,ophthalmoplegia,peripheral neuropathy,and others.Except agenesis of the corpus callosum and periventricular white matter changes,patients might show cortical atrophy,ventricular dilation,and cerebellar atrophy,and so on.Chinese SPG11 patients manifested significant clinical and genetical heterogeneity and no obvious gender difference.Of them,37 pathogenic mutations of KIAA1840 gene were detected,which all introduced truncated mutation of spatacsin protein.KIAA1840 gene frameshift mutation is the most common type of mutation.

关 键 词：遗传性痉挛性截瘫11型 基因突变 常染色体隐性遗传 KIAA1840基因 spatacsin 

分 类 号：R741[医药卫生—神经病学与精神病学]