研究报告

肌萎缩侧索硬化患者SOD1基因突变检测及突变与临床表型的关系

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  • 1. 福建医科大学附属第一医院神经内科, 福州350005 2. 复旦大学附属华山医院神经内科, 上海 200040

收稿日期: 2010-12-28

  修回日期: 2011-04-15

  网络出版日期: 2011-07-25

基金资助

福建省高校创新团队培育计划项目(编号:FMU-RT002)资助

Screening of mutations in SOD1 gene and analysis of geno-type-phenotype correlation in Chinese patients with amyotrophic lateral sclerosis

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  • 1. Department of Neurology, First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, China 2. Department of Neurology, Huashan Hospital, Fudan University, Shanghai 200040, China

Received date: 2010-12-28

  Revised date: 2011-04-15

  Online published: 2011-07-25

摘要

应用PCR技术结合DNA直接测序方法对8例临床确诊为家族性肌萎缩侧索硬化(Familiar amyotrophic lateral sclerosis, FALS)家系的先证者进行铜锌超氧化物歧化酶基因(SOD1)的突变筛查, 在3例先证者中检出2种SOD1基因突变, 其中, 2例携带了位于4号外显子的错义突变Cys111Tyr(c.332G>A), 另1例携带了位于5号外显子的错义突变Gly147Asp (c.440G>A), 这2种突变在中国ALS患者中属首次报道。该结果扩大了中国FALS患者的SOD1基因突变谱, 对研究中国FALS患者SOD1基因突变特点和分布规律有一定帮助。分析携带这2个突变患者的临床特点, 提示Cys111Tyr突变导致的临床表型相对温和, 而Gly147Asp突变可导致病情进展较快。该结果有待在更多的病例中进行证实。

本文引用格式

牛艳芳,熊慧玲,邬剑军,陈嬿,乔凯,吴志英 . 肌萎缩侧索硬化患者SOD1基因突变检测及突变与临床表型的关系[J]. 遗传, 2011 , 33(7) : 720 -724 . DOI: 10.3724/SP.J.1005.2011.00720

Abstract

In this study, we screened for the Cu/Zn superoxide dismutase (SOD1) mutations in 8 probands who had been clinically diagnosed with familiar amyotrophic lateral sclerosis (FALS) using PCR and direct sequencing. Two known mu-tations were detected in the three probands. Two probands carried the same Cys111Tyr (c.332G>A) mutation in exon 4, and others carried Gly147Asp (c.440G>A) mutation in exon 5. These two mutations were first reported in the Chinese ALS patients. After reviewing all clinical data of these three pedigrees, we found that Cys111Tyr led to a relatively mild pheno-type and Gly147Asp displayed a rapidly progression, which needs to be confirmed by further study in more ALS patients. In conclusion, this study extends the spectrum of SOD1 mutations in the Chinese FALS patients and facilitates to investigate characteristics and distribution of SOD1 mutations in the Chinese population.

参考文献

[1] del Aguila MA, longstreth WT Jr, McGuire V, Koepsell TD, van Belle G. Prognosis in amyotrophic lateral sclerosis: a population-based study. Neurology, 2003, 60(5): 813-819.
[2] 陈文族, 赵振华, 吴志英. 家族性肌萎缩侧索硬化致病基因的研究进展. 中华神经科杂志, 2008, 40(6): 425-428.
[3] 史树贵, 李露斯, 陈康宁, 刘昕. 一个肌萎缩侧索硬化家系的SOD1基因突变. 中华医学遗传学杂志, 2004, 21(2): 149-152.
[4] Zhang HG, Zhao HS, Lu M, Zhang YS, Wang LP, Zhang J, Ma D, Fan DS. A rare Cu/Zn superoxide dismutase mutation causing familial amyotrophic lateral sclerosis with variable age of onset and incomplete penetrance in China. Amyotroph Lateral Scler Other Motor Neuron Disord, 2005, 6(4): 234-238.
[5] Fong GCY, Kwok KHH, Song YQ, Cheng TS, Ho PWL, Chu ACY, Kung MHW, Chan KH, Mak W, Cheung RTF, Ramsden DB, Ho SL. Clinical phenotypes of a large Chinese multigenerational kindred with autosomal dominant familial ALS due to Ile149Thr SOD1 gene mutation. Amyotroph Lateral Scler, 2006, 7(3): 142-149.
[6] Tsai CP, Soong BW, Lin KP, Tu PH, Lin JL, Lee YC. FUS, TARDBP, and SOD1 mutations in a Taiwanese cohort with familial ALS. Neurobiol Ag-ing, 2010, 32(3): 553. e13-e21.
[7] 李晓光, 张莉红, 谢曼青, 刘明生, 李本红, 赵燕环, 崔丽英. 中国家族性肌萎缩侧索硬化患者超氧化物歧化酶1基因突变分析. 中华神经科杂志, 2010, 43(10): 686-691.
[8] Brooks BR, Miller RG, Swash M, Munsat TL. World Federation of Neurology Research Group on Motor Neuron Diseases. EI Escorial revisited: revised criteria for the diagnosis of amyotrophic lateral sclerosis. Amyotroph Lateral Scler Other Motor Neuron Disord, 2000, 1(5): 593-599.
[9] Xiong HL, Wang JY, Sun YM, Wu JJ, Chen Y, Qiao K, Zheng QJ, Zhao GX, Wu ZY. Association between novel TARDBP mutations and Chinese patients with amyotrophic lateral sclerosis. BMC Med Genet, 2010, 11: 8.
[10] Chattopadhyay M, Valentine JS. Aggregation of copper-zinc superoxide dismutase in familial and sporadic ALS. Antioxid Redox Signal, 2009, 11(7): 1603-1614.
[11] Juneja T, Pericak-Vance MA, Laing NG, Dave S, Siddique T. Prognosis in familial amyotrophic lateral sclerosis: progression and survival in patients with glu100gly and ala4val mutations in Cu, Zn superoxide dismutase. Neurology, 1997, 48(1): 55-57.
[12] Saeed M, Yang Y, Deng HX, Hung WY, Siddique N, Dellefave L, Gellera C, Andersen PM, Siddique T. Age and founder effect of SOD1 A4V mutation causing ALS. Neurology, 2009, 72(19): 1634-1639.
[13] Andersen PM, Forsgren L, Binzer M, Nilsson P, Ala-Hurula V, Keränen ML, Bergmark L, Saarinen A, Haltia T, Tarvainen I, Kinnunen E, Udd B, Marklund SL. Autosomal recessive adult-onset amyotrophic lateral scle-rosis associated with homozygosity for Asp90Ala CuZn-superoxide dismutase mutation. A clinical and ge-nealogical study of 36 patients. Brain, 1996, 119(Pt4): 1153-1172.
[14] Cudkowicz ME, Mckenna-Yasek D, Sapp PE, Chin W, Geller B, Hayden DL, Schoenfeld DA, Hosler BA, Horvitz HR, Brown RH. Epidemiology of mutations in superoxide dismutase in amyotrophic lateral sclerosis. Ann Neurol, 1997, 41(2): 20-21.
[15] Eisen A, Mezei MM, Stewart HG, Fabros M, Gibson G, Andersen PM. SOD1 gene mutations in ALS patients from British Columbia, Canada: Clinical features, neurophysiology and ethical issues in management. Amyotroph Lateral Scler, 2008, 9(2): 108-119.
[16] Suzuki M, Yasui K, Ishikawai H, Nomura M, Watanabe T, Mikami H, Yamano T, Ono S. Familial amyotrophic lateral sclerosis with Cys111Tyr mutation in Cu/Zn superoxide dismutase showing widespread Lewy body-like hyaline inclusions. J Neurol Sci, 2011, 300(1-2): 182-184.
[17] Andersen PM. Amyotrophic lateral sclerosis genetics with mendelian inheritance//Brown RH, Swash M, Pasinelli P, eds. Amyotroph Lateral Scler. 2 nd ed. London: Informa Healthcare, 2006: 187-207.
[18] Millecamps S, Salachas F, Cazeneuve C, Gordon P, Bricka B, Camuzat A, Guillot-Noël L, Russaouen O, Br
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