Mutations in the colony stimulating factor 1 receptor (CSF1R) gene cause hereditary diffuse leukoencephalopathy with spheroids (original) (raw)

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Acknowledgements

We thank all family members who participated in this study, D. Gamble for help in coordinating sample and data collection from subjects with ischemic stroke, and R. Ossi for review of brain MRI scans from subjects with ischemic stroke. This work is funded by a Mayo Benefactor and the Mayo Foundation. Mayo Clinic Jacksonville is a Morris K. Udall Parkinson's Disease Research Center of Excellence supported by the US National Institute of Neurological Disorders and Stroke (P50 NS072187). Z.K.W. is partially funded by the US National Institutes of Health (NIH; R01 NS057567 and 1RC2NS070276) and by Mayo Clinic Florida CR programs (MCF 90052018 and MCF 90052030). Z.K.W. is further supported by the family of Carl Edward Bolch Jr. and Susan Bass Bolch, and by Dystonia Medical Research Foundation. R.R. is funded by NIH grants R01 NS065782, R01 AG026251 and P50 AG016574 and by the Peebler PSP Research Foundation. O.A.R. is supported by the American Heart Association, the James & Esther King Biomedical Research Program, the Florida Department of Health and the Myron and Jane Hanley Award in Stroke research. C.W. is supported by the Leenaards Foundation and the Swiss Parkinson Foundation. The Mayo Clinic Florida Cerebrovascular Diseases Registry (IRB no. 08-003878; J.F.M., Principal Investigator) is supported by the Mayo Foundation for Medical Education and Research. C.S. is supported by grants from Sven and Dagmar Saléns, Stiftelse, Sweden; the Swedish and Gothenburg Societies for the Neurologically Disabled; The Swedish Society of Medicine Gothenburg; the Gothenburg Foundation for Neurological Research; and the Björnsson Foundation, Gothenburg, Sweden. This work is further funded by NIH PHS P30 AG 10133 (Indiana Alzheimer Disease Center, to B.G.) and NIH U24 AG 21886-01S1 (National Cell Repository for Alzheimer's disease, to B.G.).

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Authors and Affiliations

1. Department of Neuroscience, Mayo Clinic Florida, Jacksonville, Florida, USA
   Rosa Rademakers, Matt Baker, Alexandra M Nicholson, Nicola J Rutherford, NiCole Finch, Alexandra Soto-Ortolaza, Christian Wider, Aleksandra Wojtas, Mariely DeJesus-Hernandez, Jennifer Adamson, Naomi Kouri, Christina Sundal, Pritam Das, Owen A Ross & Dennis W Dickson
2. Department of Neurology, Mayo Clinic Florida, Jacksonville, Florida, USA
   Jennifer Lash, Elizabeth A Shuster, Ryan Uitti, Jay A Van Gerpen, James F Meschia, Neill Graff-Radford & Zbigniew K Wszolek
3. Department of Clinical Neurosciences, Centre Hospitalier Universitaire Vaudois (CHUV-UNIL), Lausanne, Switzerland
   Christian Wider
4. Department of Clinical Neuroscience and Rehabilitation, Institute of Neuroscience and Physiology, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden
   Christina Sundal
5. Department of Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway
   Jan Aasly
6. Department of Pathology, University of Aberdeen, Aberdeen, Scotland, UK
   James MacKenzie
7. Center for Neuropathology and Prion Research, Ludwig-Maximilians Universität Munich, Munich, Germany
   Sigrun Roeber & Hans A Kretzschmar
8. Department of Neurology, Mayo Clinic Minnesota, Rochester, Minnesota, USA
   Bradley F Boeve, David S Knopman & Ronald C Petersen
9. Department of Neurology, Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, Missouri, USA
   Nigel J Cairns
10. Department of Pathology and Laboratory Medicine, Indiana Alzheimer Disease Center, Indiana University School of Medicine, Indianapolis, Indiana, USA
    Bernardino Ghetti & Salvatore Spina
11. Department of Neurology, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA
    James Garbern
12. Department of Neurology, Wayne State University School of Medicine, Detroit, Michigan, USA
    Alexandros C Tselis
13. HudsonAlpha Institute for Biotechnology, Huntsville, Alabama, USA
    Shawn Levy
14. Department of Radiology, Mayo Clinic Florida, Jacksonville, Florida, USA
    Daniel F Broderick
15. Department of Pathology, Texas Tech University Health Sciences Center, Lubbock, Texas, USA
    Bradley B Miller
16. Department of Neurology, University of Kansas School of Medicine, Kansas City, Kansas, USA
    Russell H Swerdlow

Authors

1. Rosa Rademakers
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2. Matt Baker
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3. Alexandra M Nicholson
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4. Nicola J Rutherford
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5. NiCole Finch
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6. Alexandra Soto-Ortolaza
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7. Jennifer Lash
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8. Christian Wider
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9. Aleksandra Wojtas
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10. Mariely DeJesus-Hernandez
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11. Jennifer Adamson
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12. Naomi Kouri
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13. Christina Sundal
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14. Elizabeth A Shuster
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15. Jan Aasly
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16. James MacKenzie
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17. Sigrun Roeber
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18. Hans A Kretzschmar
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19. Bradley F Boeve
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20. David S Knopman
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21. Ronald C Petersen
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22. Nigel J Cairns
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23. Bernardino Ghetti
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24. Salvatore Spina
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25. James Garbern
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26. Alexandros C Tselis
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27. Ryan Uitti
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28. Pritam Das
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29. Jay A Van Gerpen
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30. James F Meschia
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31. Shawn Levy
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32. Daniel F Broderick
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33. Neill Graff-Radford
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34. Owen A Ross
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35. Bradley B Miller
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36. Russell H Swerdlow
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37. Dennis W Dickson
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38. Zbigniew K Wszolek
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Contributions

R.R. and Z.K.W. directed the study. R.R., M.B. and A.M.N. wrote the manuscript. M.B. directed the genetic studies and performed the linkage analysis. A.M.N. directed the functional studies. S.L. performed the exome sequencing and variant calling analysis. M.B., N.J.R., A.S.-O., O.A.R. and A.W. performed the gene sequencing and genotyping studies. A.M.N., N.F., A.W., N.K. and P.D. performed the mutagenesis, cell biology and protein biochemistry studies. Z.K.W. directed the international consortium, assisted by J.L., C.W., C.S., M.D.-H. and J.A. E.A.S., J.A., J.M., S.R., H.A.K., N.J.C., B.G., S.S., A.C.T., J.G., J.A.V.G., B.F.B., D.S.K., R.C.P., D.F.B., J.F.M., R.U., N.G.-R., R.H.S., B.B.M., D.W.D. and Z.K.W. performed clinical evaluations. B.B.M. performed radiological studies. D.W.D. performed neuropathological studies. All authors contributed to manuscript revision.

Corresponding author

Correspondence toRosa Rademakers.

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The authors declare no competing financial interests.

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Rademakers, R., Baker, M., Nicholson, A. et al. Mutations in the colony stimulating factor 1 receptor (CSF1R) gene cause hereditary diffuse leukoencephalopathy with spheroids.Nat Genet 44, 200–205 (2012). https://doi.org/10.1038/ng.1027

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• Received: 11 July 2011
• Accepted: 04 November 2011
• Published: 25 December 2011
• Issue Date: February 2012
• DOI: https://doi.org/10.1038/ng.1027