Mutations in UBQLN2 cause dominant X-linked juvenile and adult-onset ALS and ALS/dementia (original) (raw)

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Acknowledgements

This study was supported by the National Institute of Neurological Disorders and Stroke (NS050641), the Les Turner ALS Foundation, the Vena E. Schaff ALS Research Fund, the Harold Post Research Professorship, the Herbert and Florence C. Wenske Foundation, the David C. Asselin MD Memorial Fund, the Help America Foundation and the Les Turner ALS Foundation/Herbert C. Wenske Foundation Professorship. F.F. has support from NIH (T32 AG20506). K.A. is a postdoctoral fellow of the Blazeman Foundation for ALS. G.H.G. received travel funds from MND Scotland. We thank N. Dantuma for the UPS reporter plasmid (through Addgene) and the staff of the Northwestern University Robert H. Lurie Comprehensive Cancer Center flow cytometry core facility for technical assistance. Imaging work was performed at the Northwestern University Cell Imaging Facility, supported by NCI CCSG P30 CA060553 awarded to the Robert H Lurie Comprehensive Cancer Center.

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Author notes

1. Seong-Tshool Hong, George H. Gorrie, Hujun Jiang & Makito Hirano
   Present address: 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.).,
2. Han-Xiang Deng and Wenjie Chen: These authors contributed equally to this work.

Authors and Affiliations

1. Division of Neuromuscular Medicine, Davee Department of Neurology and Clinical Neurosciences, Northwestern University Feinberg School of Medicine, Chicago, 60611, Illinois, USA
   Han-Xiang Deng, Wenjie Chen, Seong-Tshool Hong, George H. Gorrie, Nailah Siddique, Yi Yang, Faisal Fecto, Yong Shi, Hong Zhai, Hujun Jiang, Makito Hirano, Sandra Donkervoort, Kaouther Ajroud, Robert L. Sufit & Teepu Siddique
2. Department of Pediatrics, University of Ottawa and Children’s Hospital of Eastern Ontario Research Institute, Ottawa, Ontario K1H 8L1, Canada
   Kym M. Boycott
3. Interdepartmental Neuroscience Program, Northwestern University Feinberg School of Medicine, Chicago, 60611, Illinois, USA
   Faisal Fecto, Enrico Mugnaini & Teepu Siddique
4. John P. Hussman Institute for Human Genomics, University of Miami, Miller School of Medicine, Miami, 33136, Florida, USA
   Evadnie Rampersaud & Margaret A. Pericak-Vance
5. Division of Anatomic Pathology, The Ottawa Hospital, Ottawa, Ontario K1Y 4E9, Canada
   Gerard H. Jansen
6. Division of Neuropathology, Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, 60611, Illinois, USA
   Eileen H. Bigio
7. Department of Neurology, Neuroscience and Spine Institute, Carolinas Medical Center, Charlotte, 28207, North Carolina, USA
   Benjamin R. Brooks
8. Center for Human Genetics Research, Vanderbilt University, Nashville, 37232, Tennessee, USA
   Jonathan L. Haines
9. Department of Cell and Molecular Biology, Northwestern University Feinberg School of Medicine, Chicago, 60611, Illinois, USA
   Enrico Mugnaini & Teepu Siddique

Authors

1. Han-Xiang Deng
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2. Wenjie Chen
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3. Seong-Tshool Hong
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4. Kym M. Boycott
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5. George H. Gorrie
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6. Nailah Siddique
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7. Yi Yang
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8. Faisal Fecto
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9. Yong Shi
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10. Hong Zhai
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11. Hujun Jiang
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12. Makito Hirano
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13. Evadnie Rampersaud
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14. Gerard H. Jansen
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15. Sandra Donkervoort
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16. Eileen H. Bigio
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17. Benjamin R. Brooks
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18. Kaouther Ajroud
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19. Robert L. Sufit
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20. Jonathan L. Haines
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21. Enrico Mugnaini
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22. Margaret A. Pericak-Vance
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23. Teepu Siddique
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Contributions

T.S. conceived and supervised this project. W.C., S.-T.H., Y.Y., H.J., M.H., H.-X.D. and T.S. did the sequencing analysis. S.T.H., E.R., J.L.H., M.P.-V. and T.S. performed linkage analysis. K.M.B., G.H.G., F.F., G.H.J., H.Z., E.H.B., K.A., E.M., H.-X.D. and T.S. performed immunohistochemical, confocal and pathological analysis. F.F., Y.S. and H.-X.D. performed functional analysis. N.S., S.D. and T.S. collected family information and coordinated this study. K.M.B., G.H.J., B.R.B., R.L.S. and T.S. did clinical studies. H.-X.D. and T.S. analysed the data and wrote the paper.

Corresponding author

Correspondence toTeepu Siddique.

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The authors declare no competing financial interests.

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Deng, HX., Chen, W., Hong, ST. et al. Mutations in UBQLN2 cause dominant X-linked juvenile and adult-onset ALS and ALS/dementia.Nature 477, 211–215 (2011). https://doi.org/10.1038/nature10353

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• Received: 20 November 2010
• Accepted: 05 July 2011
• Published: 21 August 2011
• Issue Date: 08 September 2011
• DOI: https://doi.org/10.1038/nature10353