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Journal of Neurology

, Volume 259, Issue 6, pp 1039–1044 | Cite as

Sporadic juvenile amyotrophic lateral sclerosis caused by mutant FUS/TLS: possible association of mental retardation with this mutation

  • Satoshi Yamashita
  • Akira Mori
  • Hideya Sakaguchi
  • Tomohiro Suga
  • Daijirou Ishihara
  • Akihiko Ueda
  • Taro Yamashita
  • Yasushi Maeda
  • Makoto Uchino
  • Teruyuki Hirano
Original Communication

Abstract

We present two cases of patients with juvenile amyotrophic lateral sclerosis (ALS), who had no history of familial ALS. The symptoms of both patients started as weakness of the unilateral upper limb and neck, and extended to bulbar and respiratory weakness in a relatively short period. Of note, the first patient was mentally retarded before the onset of weakness. Fused in sarcoma/translocated in liposarcoma (FUS/TLS) gene analyses revealed mutations of p. G492EfsX527 (c. 1475delG), which is a novel deletion/frameshift mutation, in the first patient and p. R514S mutation (c. 1542G > T) in the second patient. Molecular analysis revealed that the mutant FUS/TLS, especially the deletion/frameshift mutation, showed significant cytoplasmic localization in transfected motor neuron-like cells. Our findings suggest the association of mental retardation with the FUS/TLS mutation. Further investigation, including the effect of FUS/TLS on cognitive function, would aid better understanding of FUS/TLS proteinopathies.

Keywords

Juvenile amyotrophic lateral sclerosis Fused in sarcoma/translocated in liposarcoma Deletion/frameshift Cytoplasmic localization Mental retardation Cognitive function 

Notes

Acknowledgments

We would like to thank Drs. Ohyagi and Fukunaga (Kyushu University, Department of Neurology) for providing NSC-34 cells.

Conflict of interest

The authors declare that there are no conflicts of interest. The authors are fully responsible for the content and writing of the paper.

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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Satoshi Yamashita
    • 1
  • Akira Mori
    • 1
    • 3
  • Hideya Sakaguchi
    • 1
  • Tomohiro Suga
    • 1
    • 3
  • Daijirou Ishihara
    • 2
  • Akihiko Ueda
    • 1
  • Taro Yamashita
    • 1
  • Yasushi Maeda
    • 1
  • Makoto Uchino
    • 1
    • 3
  • Teruyuki Hirano
    • 1
  1. 1.Department of Neurology, Faculty of Life SciencesKumamoto UniversityKumamotoJapan
  2. 2.Department of NeurologyOmuta Tenryo HospitalOmutaJapan
  3. 3.Department of NeurologyJonan Hospital, MainoharaJonanJapan

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