遗传性痉挛性截瘫11型基因突变分析  

Mutations analysis of SPG11 gene in Chinese Han patients with hereditary spastic paraplegia

作　　者：杜鹃[1] 廖书胜[2] 胡雅岑[1] 陈冲[1] 罗莹莹[1] 王银光[1] 江泓[1] 唐北沙[1] 沈璐[1] 

机构地区：[1]中南大学湘雅医院神经内科,长沙410008 [2]广西壮族自治区柳州市人民医院神经内科

出　　处：《中华神经科杂志》2010年第7期499-504,共6页Chinese Journal of Neurology

基　　金：国家＂十五＂科技攻关计划课题资助项目（2004BA720A03）;国家＂十一五＂支撑重大项目资助项目（2006BA105A07）;国家自然科学基金资助项目（30671151）;湖南省杰出青年基金资助项目（2007JJ1005）

摘　　要：目的 探讨中国人群遗传性痉挛性截瘫11型（SPGll）基因突变频率及临床特点.方法 应用聚合酶链反应（PCR）结合直接测序方法对28个常染色体隐性遗传性痉挛性截瘫（ARHSP）家系先证者和14例散发痉挛性截瘫合并胼胝体发育不良患者进行SPG11基因突变分析.结果 共确诊10例SPG11家系,其中7个为ARHSP家系,3例为散发患者,共携带有13个SPG11基因新突变：c.5977C〉T/p.Q1993X、c.4668T〉A/p.Y1556X、c.6898_6899delCT/p.L2300AfsX23.38、c.3719_3720delTA/p.11240VfsX263、c.733_734delAT/p.M245VfsX246、c.7088_7089insATTA/p.Y2363X、c.2163_2164insT/p.1722Yfsx731、c.7101-7102insT/p.K2368X、c.6790_6791insC/p.12264PfsX2339、c.654_655delinsG/p.S218RfsX219、c.7151＋4_7151＋7delAGTA/p.K2384fsX2386、c.6355-21_6355-18delTCT、c.3004C〉T/p.G1002X.SPG11在ARHSP家系的发病率约为25.0%（7/28）,在ARHSP合并胼胝体发育不良（ARHSP-TCC）家系的发病率为6/6,在散发HSP-TCC患者中突变率为3/14.结论 对于中国人群而言,复杂型ARHSP和散发HSP-TCC患者应首先排除SPG11基因突变.Objective To identify disease-causing mutations in a large panel of Chinese Han patients with hereditary spastic paraplegia（HSP）.Methods The coding sequence of the SPG11 gene in the probands of 28 families with ARHSP and 14 sporadic HSP patients was analyzed,and the identified changes in the sequence were tested to exclude being a benign polymorphism by sequencing 200 chromosomes from normal controls.Results Identified 13 causative mutations in SPG11 gene in 7 ARHSP and 3 sporadic HSP The mutations were：c.5977C〉T/p.Q1993X、c.4668T〉A/p.Y1556X、c.6898_6899delCT/p.L2300AfsX23.38、c.3719_3720delTA/p.11240VfsX263、c.733_734delAT/p.M245VfsX246、c.7088_7089insATTA/p.Y2363X、c.2163_2164insT/p.1722Yfsx731、c.7101-7102insT/p.K2368X、c.6790_6791insC/p.12264PfsX2339、c.654_655delinsG/p.S218RfsX219、c.7151＋4_7151＋7delAGTA/p.K2384fsX2386、c.6355-21_6355-18delTCT、c.3004C〉T/p.G1002X.Among them,12 were novel mutations.The rate of mutation in the SPG11 gene was 25.0%（7/28）in ARHSP,6/6 in ARHSP-TCC and 3/14 in sporadic cases.Conclusions In Chinese Han population,patients with ARHSP-TCC and sporadic HSP-TCC should be screened for SPG11.Sequencing of the SPG11 gene in these patients with is valuable for clinical diagnostic testing.

关 键 词：痉挛性截瘫 遗传性 突变 蛋白质类 

分 类 号：R741[医药卫生—神经病学与精神病学]