散发性肌萎缩侧索硬化遗传学研究进展_West China Medical Journal

Authors：

方登富 ¹ ,  曾艳 ²

Corresponding author：

曾艳, Email: fander448@163.com

Keywords：

肌萎缩侧索硬化; 散发性; 遗传学

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【摘要】　肌萎缩侧索硬化是一种成年起病、选择性侵犯运动神经元的神经系统慢性进展性变性疾病。约90%的患者为散发性，病因及发病机制尚未完全清楚，目前研究认为是多因素包括遗传因素和环境因素共同作用的结果。尽管目前未发现某一个单独的基因可导致散发性肌萎缩侧索硬化的发生，但近年随着全基因组关联研究方法的采用，发现了部分基因与之相关。现就近来散发性肌萎缩侧索硬化的分子遗传学研究进展作一综述。

Citation： 方登富,曾艳. 散发性肌萎缩侧索硬化遗传学研究进展. West China Medical Journal, 2011, 26(4): 629-631. doi: Copy

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14.	Igaz LM, Kwong LK, Chen-Plotkin A, et al. Expression of TDP-43 C-terminal Fragments in Vitro Recapitulates Pathological Features of TDP-43 Proteinopathies[J]. J Biol Chem, 2009, 284(13): 8516-8524.
15.	Mackenzie IR, Bigio EH, Ince PG, et al. Pathological TDP-43 distinguishes sporadic amyotrophic lateral sclerosis from amyotrophic lateral sclerosis with SOD1 mutations[J]. Ann Neurol, 2007, 61(5): 427-434.
16.	Maekawa S, Leigh PN, King A, et al. TDP-43 is consistently co-localized with ubiquitinated inclusions in sporadic and Guam amyotrophic lateral sclerosis but not in familial amyotrophic lateral sclerosis with and without SOD1 mutations[J]. Neuropathology, 2009, 29(6): 672-683.
17.	Corrado L, Ratti A, Gellera C, et al. High frequency of TARDBP gene mutations in Italian patients with amyotrophic lateral sclerosis[J]. Hum Mutat, 2009, 30(4): 688-694.
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19.	Liscic RM, Grinberg LT, Zidar J, et al. ALS and FTLD: two faces of TDP-43 proteinopathy[J]. Eur J Neurol, 2008, 15(8): 772-780.
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28.	van Es MA, van vught PW, Blauw HM, et al. Genetic variation in DPP6 is associated with susceptibility to amyotrophic lateral sclerosis[J]. Nat Genet, 2008, 40(1): 29-31.
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30.	Burghes AH, Butchbach ME. Let all DNA vote: who are the amyotrophic lateral sclerosis candidates?[J]. Neurology, 2008, 70(9): 662-663.
31.	Dupré N, Valdmanis P. Genome-wide association studies in amyotrophic lateral sclerosis[J]. Eur J Hum Genet, 2009, 17(2): 137-138.
32.	Fernandez-Santiago R, Sharma M, Berg D, et al. No evidence of association of FLJ10986 and ITPR2 with ALS in a large German cohort[J]. Neurobiol Aging, 2011,32(3): 551.
33.	Schymick JC, Talbot K, Traynor BJ. Genetics of sporadic amyotrophic lateral sclerosis[J]. Hum Mol Genet, 2007, 16(Spec 2): 233-242.

1. 　Mitchell JD, Borasio GD. Amyotrophic lateral sclerosis[J]. Lancet, 2007, 369(9578): 2031-2041.
2. 　Rosen DR, Siddique T, Patterson D, et al. Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis[J]. Nature, 1993, 362(6415): 59-62.
3. 　Beleza-Meireles A, Al-Chalabi A. Genetic studies of amyotrophic lateral sclerosis: controversies and perspectives[J]. Amyotroph Lateral Scler, 2009, 10(1): 1-14.
4. 　Siddique T, Figlewicz DA, Pericak-Vance MA, et al. Linkage of a gene causing familial amyotrophic lateral sclerosis to chromosome 21 and evidence of genetic-locus heterogeneity[J]. N Engl J Med, 1991, 324(20): 1381-1384.
5. 　Jones CT, Brock DJ, Chancellor AM, et al. Cu/Zn superoxide dismutase (SOD1) mutations and sporadic amyotrophic lateral sclerosis[J]. Lancet, 1993, 342(8878): 1050-1051.
6. 　Gruzman A, Wood WL, Alpert E, et al. Common molecular signature in SOD1 for both sporadic and familial amyotrophic lateral sclerosis[J]. Proc Natl Acad Sci USA, 2007, 104(30): 12524-12529.
7. 　Orrell RW, Figlewicz DA. Clinical implications of the genetics of ALS and other motor neuron diseases[J]. Neurology, 2001, 57(1): 9-17.
8. 　Gros-Louis F, Gaspar C, Rouleau GA. Genetics of familial and sporadic amyotrophic lateral sclerosis[J]. Biochim Biophys Acta, 2006, 1762(11-12): 956-972.
9. 　Gellera C, Castellotti B, Riggio MC, et al. Superoxide dismutase gene mutations in Italian patients with familial and sporadic amyotrophic lateral sclerosis: identification of three novel missense mutations[J]. Neuromuscul Disord, 2001, 11(4): 404-410.
10. 　Orrell RW, Habgood J, Rudge P, et al. Difficulties in distinguishing sporadic from familial amyotrophic lateral sclerosis[J]. Ann Neurol, 1996, 39(6): 810-812.
11. 　Cleveland DW, Rothstein JD. From Charcot to Lou Gehrig: deciphering selective motor neuron death in ALS[J]. Nat Rev Neurosci, 2001, 2(11): 806-819.
12. 　Arai T, Hasegawa M, Akiyama H, et al. TDP-43 is a component of ubiquitin-positive tau-negative inclusions in frontotemporal lobar degeneration and amyotrophic lateral sclerosis[J]. Biochem Biophys Res Commun, 2006, 351(3): 602-611.
13. 　Neumann M, Sampathu DM, Kwong LK, et al. Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis[J]. Science, 2006, 314(5796): 130-133.
14. 　Igaz LM, Kwong LK, Chen-Plotkin A, et al. Expression of TDP-43 C-terminal Fragments in Vitro Recapitulates Pathological Features of TDP-43 Proteinopathies[J]. J Biol Chem, 2009, 284(13): 8516-8524.
15. 　Mackenzie IR, Bigio EH, Ince PG, et al. Pathological TDP-43 distinguishes sporadic amyotrophic lateral sclerosis from amyotrophic lateral sclerosis with SOD1 mutations[J]. Ann Neurol, 2007, 61(5): 427-434.
16. 　Maekawa S, Leigh PN, King A, et al. TDP-43 is consistently co-localized with ubiquitinated inclusions in sporadic and Guam amyotrophic lateral sclerosis but not in familial amyotrophic lateral sclerosis with and without SOD1 mutations[J]. Neuropathology, 2009, 29(6): 672-683.
17. 　Corrado L, Ratti A, Gellera C, et al. High frequency of TARDBP gene mutations in Italian patients with amyotrophic lateral sclerosis[J]. Hum Mutat, 2009, 30(4): 688-694.
18. 　Daoud H, Valdmanis PN, Kabashi E, et al. Contribution of TARDBP mutations to sporadic amyotrophic lateral sclerosis[J]. J Med Genet, 2009, 46(2): 112-114.
19. 　Liscic RM, Grinberg LT, Zidar J, et al. ALS and FTLD: two faces of TDP-43 proteinopathy[J]. Eur J Neurol, 2008, 15(8): 772-780.
20. 　Kabashi E, Valdmanis PN, Dion P, et al. TARDBP mutations in individuals with sporadic and familial amyotrophic lateral sclerosis[J]. Nat Genet, 2008, 40(5): 572-574.
21. 　Sreedharan J, Blair IP, Tripathi VB, et al. TDP-43 mutations in familial and sporadic amyotrophic lateral sclerosis[J]. Science, 2008, 319(5870): 1668-1672.
22. 　van Deerlin VM, Leverenz JB, Bekris LM, et al. TARDBP mutations in amyotrophic lateral sclerosis with TDP-43 neuropathology: a genetic and histopathological analysis[J]. Lancet Neurol, 2008, 7(5): 409-416.
23. 　Lagier-Tourenne C, Cleveland DW. Rethinking ALS: the FUS about TDP-43[J]. Cell, 2009, 136(6): 1001-1004.
24. 　Schymick JC, Scholz SW, Fung HC, et al. Genome-wide genotyping in amyotrophic lateral sclerosis and neurologically normal controls: first stage analysis and public release of data[J]. Lancet Neurol, 2007, 6(4): 322-328.
25. 　Dunckley T, Huentelman MJ, Craig DW, et al. Whole-genome analysis of sporadic amyotrophic lateral sclerosis[J]. N Engl J Med, 2007, 357(8): 775-788.
26. 　van Es MA, Van Vught PW, Blauw HM, et al. ITPR2 as a susceptibility gene in sporadic amyotrophic lateral sclerosis: a genome-wide association study[J]. Lancet Neurol, 2007, 6(10): 869-877.
27. 　Kasperaviciute D, Weale ME, Shianna KV, et al. Large-scale pathways-based association study in amyotrophic lateral sclerosis[J]. Brain, 2007, 130(Pt 9): 2292-2301.
28. 　van Es MA, van vught PW, Blauw HM, et al. Genetic variation in DPP6 is associated with susceptibility to amyotrophic lateral sclerosis[J]. Nat Genet, 2008, 40(1): 29-31.
29. 　van Es MA, Van Vught PW, Veldink JH, et al. Analysis of FGGY as a risk factor for sporadic amyotrophic lateral sclerosis[J]. Amyotroph Lateral Scler, 2009,10(5-6):441-447.
30. 　Burghes AH, Butchbach ME. Let all DNA vote: who are the amyotrophic lateral sclerosis candidates?[J]. Neurology, 2008, 70(9): 662-663.
31. 　Dupré N, Valdmanis P. Genome-wide association studies in amyotrophic lateral sclerosis[J]. Eur J Hum Genet, 2009, 17(2): 137-138.
32. 　Fernandez-Santiago R, Sharma M, Berg D, et al. No evidence of association of FLJ10986 and ITPR2 with ALS in a large German cohort[J]. Neurobiol Aging, 2011,32(3): 551.
33. 　Schymick JC, Talbot K, Traynor BJ. Genetics of sporadic amyotrophic lateral sclerosis[J]. Hum Mol Genet, 2007, 16(Spec 2): 233-242.

West China Medical Journal

散发性肌萎缩侧索硬化遗传学研究进展

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