Mutations in the colony stimulating factor 1 receptor (CSF1R) gene cause hereditary diffuse leukoencephalopathy with spheroids
| العنوان: | Mutations in the colony stimulating factor 1 receptor (CSF1R) gene cause hereditary diffuse leukoencephalopathy with spheroids |
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| المؤلفون: | Daniel F. Broderick, Nicole A. Finch, Matt Baker, Alexandra I. Soto-Ortolaza, Nicola J. Rutherford, Aleksandra Wojtas, Hans A. Kretzschmar, Jennifer Adamson, Jan O. Aasly, Rosa Rademakers, Bradley F. Boeve, Jay A. van Gerpen, Neill R. Graff-Radford, Alexandros Tselis, Zbigniew K. Wszolek, James Y. Garbern, James F. Meschia, Naomi Kouri, Russell H. Swerdlow, Bernardino Ghetti, Ryan J. Uitti, Pritam Das, Ronald C. Petersen, Owen A. Ross, Mariely DeJesus-Hernandez, Jennifer Lash, Nigel J. Cairns, Elizabeth A. Shuster, Christian Wider, Alexandra M. Nicholson, Sigrun Roeber, James MacKenzie, Dennis W. Dickson, Bradley Miller, Christina Sundal, Salvatore Spina, David S. Knopman, Shawn Levy |
| المصدر: | Nature genetics Nature Genetics, vol. 44, no. 2, pp. 200-205 |
| بيانات النشر: | Springer Science and Business Media LLC, 2011. |
| سنة النشر: | 2011 |
| مصطلحات موضوعية: | Adult, Male, Adolescent, Genetic Linkage, Molecular Sequence Data, Receptor, Macrophage Colony-Stimulating Factor, Biology, medicine.disease_cause, Article, Colony stimulating factor 1 receptor, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Genetics, medicine, Humans, Exome, Phosphorylation, Exome sequencing, Aged, 030304 developmental biology, Aged, 80 and over, 0303 health sciences, Mutation, Base Sequence, Parkinsonism, Autophosphorylation, Sequence Analysis, DNA, Middle Aged, Protein-Tyrosine Kinases, medicine.disease, Leukodystrophy, Globoid Cell, 3. Good health, Protein kinase domain, Cancer research, Hereditary diffuse leukoencephalopathy with spheroids, Female, Human medicine, Tyrosine kinase, 030217 neurology & neurosurgery |
| الوصف: | Hereditary diffuse leukoencephalopathy with spheroids (HDLS) is an autosomal dominantly inherited central nervous system white matter disease with variable clinical presentations including personality and behavioral changes, dementia, depression, parkinsonism, seizures, and others1,2. We combined genome-wide linkage analysis with exome sequencing and identified 14 different mutations affecting the tyrosine kinase domain of the colony stimulating factor receptor 1 (encoded by CSF1R) in 14 families affected by HDLS. In one kindred, the de novo occurrence of the mutation was confirmed. Follow-up sequencing analyses identified an additional CSF1R mutation in a patient clinically diagnosed with corticobasal syndrome (CBS). In vitro, CSF-1 stimulation resulted in the rapid autophosphorylation of selected tyrosine-residues in the kinase domain of wild-type but not mutant CSF1R, suggesting that HDLS may result from a partial loss of CSF1R function. Since CSF1R is a critical mediator of microglial proliferation and differentiation in the brain, our findings suggest an important role for microglial dysfunction in HDLS pathogenesis. |
| وصف الملف: | application/pdf |
| تدمد: | 1546-1718 1061-4036 |
| DOI: | 10.1038/ng.1027 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0e7f243086ef6c150273b9f8fc2c6edb https://doi.org/10.1038/ng.1027 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....0e7f243086ef6c150273b9f8fc2c6edb |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15461718 10614036 |
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| DOI: | 10.1038/ng.1027 |