Journal of the Neurological Sciences
Volume 296, Issue 1 , Pages 59-63 , 15 September 2010

A Japanese ALS6 family with mutation R521C in the FUS/TLS gene: A clinical, pathological and genetic report

  • Yukiko Yamamoto-Watanabe

      Affiliations

    • Department of Neurology, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori 036-8562, Japan
  • ,
  • Mitsunori Watanabe

      Affiliations

    • Department of Neurology, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori 036-8562, Japan
    • Department of Neurology, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan
    • Corresponding Author InformationCorresponding author. Department of Neurology, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori 036-8562, Japan. Tel.: +81 172 39 5142; fax: +81 172 39 5143.
  • ,
  • Koichi Okamoto

      Affiliations

    • Department of Neurology, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan
  • ,
  • Yukio Fujita

      Affiliations

    • Department of Neurology, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan
  • ,
  • Mandy Jackson

      Affiliations

    • Centre of Integrative Physiology, University of Edinburgh, Summerhall, Edinburgh, UK
  • ,
  • Masaki Ikeda

      Affiliations

    • Department of Neurology, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan
  • ,
  • Yoichi Nakazato

      Affiliations

    • Department of Human Pathology, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan
  • ,
  • Yoshio Ikeda

      Affiliations

    • Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Okayama 700-8558, Japan
  • ,
  • Etsuro Matsubara

      Affiliations

    • Department of Neurology, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori 036-8562, Japan
  • ,
  • Takeshi Kawarabayashi

      Affiliations

    • Department of Neurology, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori 036-8562, Japan
  • ,
  • Mikio Shoji

      Affiliations

    • Department of Neurology, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori 036-8562, Japan

Received 10 February 2010 ,Revised 28 May 2010 ,Accepted 7 June 2010.

References 

  1. Mitsumoto H, Chad DA, Pioro EP. Amyotrophic lateral sclerosis. Philadelphia: F.A. Davis; 1998;
  2. Cleveland DW, Rothstein JD. From Charcot to Lou Gehrig: deciphering selective motor neuron death in ALS. Nat Rev Neurosci. 2001;2:806–819
  3. Valdmanis PN, Daoud H, Dion PA, Rouleau GA. Recent advances in the genetics of amyotrophic lateral sclerosis. Curr Neurol Neurosci Rep. 2009;9:198–205
  4. Deng HX, Hentati A, Tainer JA, Iqbal Z, Cayabyab A, Hung WY, et al. Amyotrophic lateral sclerosis and structural defects in Cu, Zn superoxide dismutase. Science. 1993;261:1047–1051
  5. Rosen DR, Siddique T, Patterson D, Figlewicz DA, Sapp P, Hentati A, et al. Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature. 1993;362:59–62
  6. Kwiatkowski TJ, Bosco DA, Leclerc AL, Tamrazian E, Vanderburg CR, Russ C, et al. Mutations in the FUS/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosis. Science. 2009;323:1205–1208
  7. Vance C, Rogelj B, Hortobagyi T, De Vos KJ, Nishimura AL, Sreedharan J, et al. Mutations in FUS, an RNA processing protein, cause familial amyotrophic lateral sclerosis type 6. Science. 2009;323:1208–1211
  8. Nishimura AL, Mitne-Neto M, Silva HC, Richieri-Costa A, Middleton S, Cascio D, et al. A mutation in the vesicle-trafficking protein VAPB causes late-onset spinal muscular atrophy and amyotrophic lateral sclerosis. Am J Hum Genet. 2004;75:822–831
  9. Greenway MJ, Andersen PM, Russ C, Ennis S, Cashman S, Donaghy C, et al. ANG mutations segregate with familial and ‘sporadic’ amyotrophic lateral sclerosis. Nat Genet. 2006;38:411–413
  10. Sreedharan J, Blair IP, Tripathi VB, Hu X, Vance C, Rogelj B, et al. TDP-43 mutations in familial and sporadic amyotrophic lateral sclerosis. Science. 2008;319:1668–1672
  11. Kabashi E, Valdmanis PN, Dion P, Spiegelman D, McConkey BJ, Vande Velde C, et al. TARDBP mutations in individuals with sporadic and familial amyotrophic lateral sclerosis. Nat Genet. 2008;40:572–574
  12. Hand CK, Khoris J, Salachas F, Gros-Louis F, Lopes AA, Mayeux-Portas V, et al. A novel locus for familial amyotrophic lateral sclerosis, on chromosome 18q. Am J Hum Genet. 2002;70:251–256
  13. Sapp PC, Hosler BA, McKenna-Yasek D, Chin W, Gann A, Genise H, et al. Identification of two novel loci for dominantly inherited familial amyotrophic lateral sclerosis. Am J Hum Genet. 2003;73:397–403
  14. Kunst CB. Complex genetics of amyotrophic lateral sclerosis. Am J Hum Genet. 2004;75:933–947
  15. Hadano S, Hand CK, Osuga H, Yanagisawa Y, Otomo A, Devon RS, et al. A gene encoding a putative GTPase regulator is mutated in familial amyotrophic lateral sclerosis 2. Nat Genet. 2001;29:166–173
  16. Yang Y, Hentati A, Deng HX, Dabbagh O, Sasaki T, Hirano M, et al. The gene encoding alsin, a protein with three guanine–nucleotide exchange factor domains, is mutated in a form of recessive amyotrophic lateral sclerosis. Nat Genet. 2001;29:160–165
  17. Chen YZ, Bennett CL, Huynh HM, Blair IP, Puls I, Irobi J, et al. DNA/RNA helicase gene mutations in a form of juvenile amyotrophic lateral sclerosis (ALS4). Am J Hum Genet. 2004;74:1128–1135
  18. Moreira MC, Klur S, Watanabe M, Nemeth AH, Le Ber I, Moniz JC, et al. Senataxin, the ortholog of a yeast RNA helicase, is mutant in ataxia-ocular apraxia 2. Nat Genet. 2004;36:225–227
  19. Puls I, Jonnakuty C, LaMonte BH, Holzbaur EL, Tokito M, Mann E, et al. Mutant dynactin in motor neuron disease. Nat Genet. 2003;33:455–456
  20. Watanabe M, Aoki M, Abe K, Shoji M, Iizuka T, Ikeda Y, et al. A novel missense point mutation (S134N) of the Cu/Zn superoxide dismutase gene in a patient with familial motor neuron disease. Hum Mutat. 1997;9:69–71
  21. Watanabe M, Jackson M, Ikeda M, Mizushima K, Amari M, Takatama M, et al. Genetic analysis of the cystatin C gene in familial and sporadic ALS patients. Brain Res. 2006;1073–1074:20–24
  22. Kadokura A, Yamazaki T, Kakuda S, Makioka K, Lemere CA, Fujita Y, et al. Phosphorylation-dependent TDP-43 antibody detects intraneuronal dot-like structures showing morphological characters of granulovacuolar degeneration. Neurosci Lett. 2009;463:87–92
  23. Stewart HG, Mackenzie IR, Eisen A, Brannstrom T, Marklund SL, Andersen PM. Clinicopathological phenotype of ALS with a novel G72C SOD1 gene mutation mimicking a myopathy. Muscle Nerve. 2006;33:701–706
  24. Ticozzi N, Silani V, LeClerc AL, Keagle P, Gellera C, Ratti A, et al. Analysis of FUS gene mutation in familial amyotrophic lateral sclerosis within an Italian cohort. Neurology. 2009;73:1180–1185
  25. Corrado L, Del Bo R, Castellotti B, Ratti A, Cereda C, Penco S, et al. Mutations of FUS gene in sporadic amyotrophic lateral sclerosis. J Med Genet. 2010;47:190–194
  26. Belzil VV, Valdmanis PN, Dion PA, Daoud H, Kabashi E, Noreau A, et al. Mutations in FUS cause FALS and SALS in French and French Canadian populations. Neurology. 2009;73:1176–1179
  27. Cudkowicz ME, McKenna-Yasek D, Sapp PE, Chin W, Geller B, Hayden DL, et al. Epidemiology of mutations in superoxide dismutase in amyotrophic lateral sclerosis. Ann Neurol. 1997;41:210–221
  28. Blair IP, Williams KL, Warraich ST, Durnall JC, Thoeng AD, Manavis J, et al. FUS mutations in amyotrophic lateral sclerosis: clinical, pathological, neurophysiological and genetic analysis. J Neurol Neurosurg Psychiatry. 2009;81:639–645
  29. Munoz DG, Neumann M, Kusaka H, Yokota O, Ishihara K, Terada S, et al. FUS pathology in basophilic inclusion body disease. Acta Neuropathol. 2009;118:617–627
  30. Neumann M, Rademakers R, Roeber S, Baker M, Kretzschmar HA, Mackenzie IR. A new subtype of frontotemporal lobar degeneration with FUS pathology. Brain. 2009;132:2922–2931

 Disclosure: The authors report no conflict of interest.

PII: S0022-510X(10)00256-X

doi: 10.1016/j.jns.2010.06.008

Journal of the Neurological Sciences
Volume 296, Issue 1 , Pages 59-63 , 15 September 2010