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Research ArticleAmyotrophic Lateral Sclerosis
Human genetics and neuropathology suggest a link between miR-218 and amyotrophic lateral sclerosis pathophysiology
- View ORCID ProfileIrit Reichenstein1,*,
- View ORCID ProfileChen Eitan1,2,*,
- View ORCID ProfileSandra Diaz-Garcia3,
- Guy Haim1,
- View ORCID ProfileIddo Magen1,
- View ORCID ProfileAviad Siany1,
- View ORCID ProfileMariah L. Hoye4,
- Natali Rivkin1,
- View ORCID ProfileTsviya Olender1,
- View ORCID ProfileBeata Toth1,
- View ORCID ProfileRevital Ravid1,
- View ORCID ProfileAmitai D. Mandelbaum1,
- View ORCID ProfileEran Yanowski1,
- View ORCID ProfileJing Liang1,
- View ORCID ProfileJeffrey K. Rymer5,6,
- View ORCID ProfileRivka Levy7,
- View ORCID ProfileGilad Beck8,
- View ORCID ProfileElena Ainbinder8,
- View ORCID ProfileSali M. K. Farhan9,10,
- View ORCID ProfileKimberly A. Lennox11,
- View ORCID ProfileNicole M. Bode11,
- View ORCID ProfileMark A. Behlke11,
- View ORCID ProfileThomas Möller12,
- View ORCID ProfileSmita Saxena13,14,
- View ORCID ProfileCristiane A. M. Moreno15,
- Giancarlo Costaguta16,
- Kristel R. van Eijk2,17,
- View ORCID ProfileHemali Phatnani18,
- View ORCID ProfileAmmar Al-Chalabi2,19,20,
- A. Nazli Başak2,21,
- View ORCID ProfileLeonard H. van den Berg2,17,
- View ORCID ProfileOrla Hardiman2,22,23,
- View ORCID ProfileJohn E. Landers2,24,
- View ORCID ProfileJesus S. Mora2,25,
- View ORCID ProfileKaren E. Morrison2,26,
- View ORCID ProfilePamela J. Shaw2,27,
- View ORCID ProfileJan H. Veldink2,17,
- View ORCID ProfileSamuel L. Pfaff16,
- Ofer Yizhar7,
- View ORCID ProfileChristina Gross5,6,
- Robert H. Brown Jr.28,
- View ORCID ProfileJohn M. Ravits3,
- View ORCID ProfileMatthew B. Harms15,
- View ORCID ProfileTimothy M. Miller4 and
- View ORCID ProfileEran Hornstein1,2,†
- 1Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 7610001, Israel.
- 2Project MinE ALS Sequencing Consortium.
- 3Department of Neurosciences, UC San Diego, La Jolla, CA 92093, USA.
- 4Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA.
- 5Division of Neurology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA.
- 6Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA.
- 7Department of Neurobiology, Weizmann Institute of Science, Rehovot 7610001, Israel.
- 8Stem Cell Core and Advanced Cell Technologies Unit, Department of Life Sciences Core Facilities, Weizmann Institute of Science, Rehovot 7610001, Israel.
- 9Analytic and Translational Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
- 10Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
- 11Integrated DNA Technologies, 1710 Commercial Park, Coralville, IA 52241, USA.
- 12Department of Neurology, School of Medicine, University of Washington, Seattle, WA 98195, USA.
- 13Department of Neurology, Inselspital University Hospital, University of Bern, Freiburgstrasse 16, CH-3010 Bern, Bern, Switzerland.
- 14Department for BioMedical Research, University of Bern, Murtenstrasse 40, CH-3008 Bern, Switzerland.
- 15Department of Neurology, Columbia University, New York, NY 10032, USA.
- 16Gene Expression Laboratory and the Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
- 17Department of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, 3584 CG, The Netherlands.
- 18Center for Genomics of Neurodegenerative Disease (CGND) and New York Genome Center (NYGC) ALS Consortium, New York, NY 10013, USA.
- 19Maurice Wohl Clinical Neuroscience Institute and United Kingdom Dementia Research Institute, Department of Basic and Clinical Neuroscience, Department of Neurology, King’s College London, London SE5 9RX, UK.
- 20Department of Neurology, King’s College Hospital, London SE5 9RS, UK.
- 21Koç University Translational Medicine Research Center, NDAL, Istanbul 34010, Turkey.
- 22Academic Unit of Neurology, Trinity College Dublin, Trinity Biomedical Sciences Institute, Dublin 2, Republic of Ireland.
- 23Department of Neurology, Beaumont Hospital, Dublin 2, Republic of Ireland.
- 24Department of Neurology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
- 25ALS Unit, Hospital San Rafael, Madrid 28016, Spain.
- 26Faculty of Medicine, University of Southampton, Southampton SO17 1BJ, UK.
- 27Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield S10 2HQ, UK.
- 28Department of Neurology, University of Massachusetts Medical School, Worcester, MA 01655, USA.
- ↵†Corresponding author. Email: eran.hornstein{at}weizmann.ac.il
↵* These authors contributed equally to this work.
See allHide authors and affiliations
Science Translational Medicine 18 Dec 2019:
Vol. 11, Issue 523, eaav5264
DOI: 10.1126/scitranslmed.aav5264
Vol. 11, Issue 523, eaav5264
DOI: 10.1126/scitranslmed.aav5264
Irit Reichenstein
1Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 7610001, Israel.
Chen Eitan
1Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 7610001, Israel.
2Project MinE ALS Sequencing Consortium.
Sandra Diaz-Garcia
3Department of Neurosciences, UC San Diego, La Jolla, CA 92093, USA.
Guy Haim
1Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 7610001, Israel.
Iddo Magen
1Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 7610001, Israel.
Aviad Siany
1Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 7610001, Israel.
Mariah L. Hoye
4Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Natali Rivkin
1Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 7610001, Israel.
Tsviya Olender
1Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 7610001, Israel.
Beata Toth
1Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 7610001, Israel.
Revital Ravid
1Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 7610001, Israel.
Amitai D. Mandelbaum
1Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 7610001, Israel.
Eran Yanowski
1Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 7610001, Israel.
Jing Liang
1Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 7610001, Israel.
Jeffrey K. Rymer
5Division of Neurology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA.
6Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA.
Rivka Levy
7Department of Neurobiology, Weizmann Institute of Science, Rehovot 7610001, Israel.
Gilad Beck
8Stem Cell Core and Advanced Cell Technologies Unit, Department of Life Sciences Core Facilities, Weizmann Institute of Science, Rehovot 7610001, Israel.
Elena Ainbinder
8Stem Cell Core and Advanced Cell Technologies Unit, Department of Life Sciences Core Facilities, Weizmann Institute of Science, Rehovot 7610001, Israel.
Sali M. K. Farhan
9Analytic and Translational Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
10Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Kimberly A. Lennox
11Integrated DNA Technologies, 1710 Commercial Park, Coralville, IA 52241, USA.
Nicole M. Bode
11Integrated DNA Technologies, 1710 Commercial Park, Coralville, IA 52241, USA.
Mark A. Behlke
11Integrated DNA Technologies, 1710 Commercial Park, Coralville, IA 52241, USA.
Thomas Möller
12Department of Neurology, School of Medicine, University of Washington, Seattle, WA 98195, USA.
Smita Saxena
13Department of Neurology, Inselspital University Hospital, University of Bern, Freiburgstrasse 16, CH-3010 Bern, Bern, Switzerland.
14Department for BioMedical Research, University of Bern, Murtenstrasse 40, CH-3008 Bern, Switzerland.
Cristiane A. M. Moreno
15Department of Neurology, Columbia University, New York, NY 10032, USA.
Giancarlo Costaguta
16Gene Expression Laboratory and the Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Kristel R. van Eijk
2Project MinE ALS Sequencing Consortium.
17Department of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, 3584 CG, The Netherlands.
Hemali Phatnani
18Center for Genomics of Neurodegenerative Disease (CGND) and New York Genome Center (NYGC) ALS Consortium, New York, NY 10013, USA.
Ammar Al-Chalabi
2Project MinE ALS Sequencing Consortium.
19Maurice Wohl Clinical Neuroscience Institute and United Kingdom Dementia Research Institute, Department of Basic and Clinical Neuroscience, Department of Neurology, King’s College London, London SE5 9RX, UK.
20Department of Neurology, King’s College Hospital, London SE5 9RS, UK.
A. Nazli Başak
2Project MinE ALS Sequencing Consortium.
21Koç University Translational Medicine Research Center, NDAL, Istanbul 34010, Turkey.
Leonard H. van den Berg
2Project MinE ALS Sequencing Consortium.
17Department of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, 3584 CG, The Netherlands.
Orla Hardiman
2Project MinE ALS Sequencing Consortium.
22Academic Unit of Neurology, Trinity College Dublin, Trinity Biomedical Sciences Institute, Dublin 2, Republic of Ireland.
23Department of Neurology, Beaumont Hospital, Dublin 2, Republic of Ireland.
John E. Landers
2Project MinE ALS Sequencing Consortium.
24Department of Neurology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Jesus S. Mora
2Project MinE ALS Sequencing Consortium.
25ALS Unit, Hospital San Rafael, Madrid 28016, Spain.
Karen E. Morrison
2Project MinE ALS Sequencing Consortium.
26Faculty of Medicine, University of Southampton, Southampton SO17 1BJ, UK.
Pamela J. Shaw
2Project MinE ALS Sequencing Consortium.
27Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield S10 2HQ, UK.
Jan H. Veldink
2Project MinE ALS Sequencing Consortium.
17Department of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, 3584 CG, The Netherlands.
Samuel L. Pfaff
16Gene Expression Laboratory and the Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Ofer Yizhar
7Department of Neurobiology, Weizmann Institute of Science, Rehovot 7610001, Israel.
Christina Gross
5Division of Neurology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA.
6Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA.
Robert H. Brown Jr.
28Department of Neurology, University of Massachusetts Medical School, Worcester, MA 01655, USA.
John M. Ravits
3Department of Neurosciences, UC San Diego, La Jolla, CA 92093, USA.
Matthew B. Harms
15Department of Neurology, Columbia University, New York, NY 10032, USA.
Timothy M. Miller
4Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Eran Hornstein
1Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 7610001, Israel.
2Project MinE ALS Sequencing Consortium.
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