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Mutations in UBQLN2 cause dominant X-linked juvenile and adult-onset ALS and ALS/dementia

Author

Listed:
  • Han-Xiang Deng

    (Northwestern University Feinberg School of Medicine)

  • Wenjie Chen

    (Northwestern University Feinberg School of Medicine)

  • Seong-Tshool Hong

    (Northwestern University Feinberg School of Medicine
    Present addresses: Laboratory of Genetics and Department of Microbiology, Chonbuk National University Medical School, Chonbuk 561-712, South Korea (S.-T.H.); Institute of Neurological Sciences, Southern General Hospital, Glasgow G51 4TF, UK (G.H.G.); Department of Health Sciences, National Natural Science Foundation of China, Beijing 100085, China (H.J.); Department of Neurology, Sakai Hospital Kinki University Faculty of Medicine, Osaka 590-0132, Japan (M.H.).)

  • Kym M. Boycott

    (University of Ottawa and Children’s Hospital of Eastern Ontario Research Institute)

  • George H. Gorrie

    (Northwestern University Feinberg School of Medicine
    Present addresses: Laboratory of Genetics and Department of Microbiology, Chonbuk National University Medical School, Chonbuk 561-712, South Korea (S.-T.H.); Institute of Neurological Sciences, Southern General Hospital, Glasgow G51 4TF, UK (G.H.G.); Department of Health Sciences, National Natural Science Foundation of China, Beijing 100085, China (H.J.); Department of Neurology, Sakai Hospital Kinki University Faculty of Medicine, Osaka 590-0132, Japan (M.H.).)

  • Nailah Siddique

    (Northwestern University Feinberg School of Medicine)

  • Yi Yang

    (Northwestern University Feinberg School of Medicine)

  • Faisal Fecto

    (Northwestern University Feinberg School of Medicine
    Northwestern University Feinberg School of Medicine)

  • Yong Shi

    (Northwestern University Feinberg School of Medicine)

  • Hong Zhai

    (Northwestern University Feinberg School of Medicine)

  • Hujun Jiang

    (Northwestern University Feinberg School of Medicine
    Present addresses: Laboratory of Genetics and Department of Microbiology, Chonbuk National University Medical School, Chonbuk 561-712, South Korea (S.-T.H.); Institute of Neurological Sciences, Southern General Hospital, Glasgow G51 4TF, UK (G.H.G.); Department of Health Sciences, National Natural Science Foundation of China, Beijing 100085, China (H.J.); Department of Neurology, Sakai Hospital Kinki University Faculty of Medicine, Osaka 590-0132, Japan (M.H.).)

  • Makito Hirano

    (Northwestern University Feinberg School of Medicine
    Present addresses: Laboratory of Genetics and Department of Microbiology, Chonbuk National University Medical School, Chonbuk 561-712, South Korea (S.-T.H.); Institute of Neurological Sciences, Southern General Hospital, Glasgow G51 4TF, UK (G.H.G.); Department of Health Sciences, National Natural Science Foundation of China, Beijing 100085, China (H.J.); Department of Neurology, Sakai Hospital Kinki University Faculty of Medicine, Osaka 590-0132, Japan (M.H.).)

  • Evadnie Rampersaud

    (John P. Hussman Institute for Human Genomics, University of Miami, Miller School of Medicine)

  • Gerard H. Jansen

    (The Ottawa Hospital)

  • Sandra Donkervoort

    (Northwestern University Feinberg School of Medicine)

  • Eileen H. Bigio

    (Northwestern University Feinberg School of Medicine)

  • Benjamin R. Brooks

    (Neuroscience and Spine Institute, Carolinas Medical Center)

  • Kaouther Ajroud

    (Northwestern University Feinberg School of Medicine)

  • Robert L. Sufit

    (Northwestern University Feinberg School of Medicine)

  • Jonathan L. Haines

    (Center for Human Genetics Research, Vanderbilt University)

  • Enrico Mugnaini

    (Northwestern University Feinberg School of Medicine
    Northwestern University Feinberg School of Medicine)

  • Margaret A. Pericak-Vance

    (John P. Hussman Institute for Human Genomics, University of Miami, Miller School of Medicine)

  • Teepu Siddique

    (Northwestern University Feinberg School of Medicine
    Northwestern University Feinberg School of Medicine
    Northwestern University Feinberg School of Medicine)

Abstract

Ubiquilin 2 pathology in ALS and ALS/dementia A study of a five-generation family with the usually fatal disorder amyotrophic lateral sclerosis (ALS) has identified mutations in the UBQLN2 gene, which encodes the ubiquitin-like protein ubiquilin 2, as a cause of ALS and ALS/dementia. This finding is of particular interest as it links familial and sporadic forms of the disease through a ubiquilin 2 pathology observed in the spinal cords of ALS cases and in the brains of ALS/dementia cases with or without UBQLN2 mutations. This novel pathology shows that abnormalities in ubiquilin 2 are associated with defects in the protein degradation pathway, abnormal protein aggregation and neurodegeneration, indicating a common pathogenic mechanism that might be a target for therapeutic intervention.

Suggested Citation

  • Han-Xiang Deng & Wenjie Chen & Seong-Tshool Hong & Kym M. Boycott & George H. Gorrie & Nailah Siddique & Yi Yang & Faisal Fecto & Yong Shi & Hong Zhai & Hujun Jiang & Makito Hirano & Evadnie Rampersau, 2011. "Mutations in UBQLN2 cause dominant X-linked juvenile and adult-onset ALS and ALS/dementia," Nature, Nature, vol. 477(7363), pages 211-215, September.
    • Handle: RePEc:nat:nature:v:477:y:2011:i:7363:d:10.1038_nature10353
    DOI: 10.1038/nature10353
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