Watson, LM;
Bamber, E;
Schnekenberg, RP;
Williams, J;
Bettencourt, C;
Lickiss, J;
Fawcett, K;
... Németh, AH; + view all
(2017)
Dominant Mutations in GRM1 Cause Spinocerebellar Ataxia Type 44.
American Journal of Human Genetics
, 101
(3)
pp. 451-458.
10.1016/j.ajhg.2017.08.005.
Preview |
Text
PIIS0002929717303270.pdf - Published Version Download (1MB) | Preview |
Abstract
The metabotropic glutamate receptor 1 (mGluR1) is abundantly expressed in the mammalian central nervous system, where it regulates intracellular calcium homeostasis in response to excitatory signaling. Here, we describe heterozygous dominant mutations in GRM1, which encodes mGluR1, that are associated with distinct disease phenotypes: gain-of-function missense mutations, linked in two different families to adult-onset cerebellar ataxia, and a de novo truncation mutation resulting in a dominant-negative effect that is associated with juvenile-onset ataxia and intellectual disability. Crucially, the gain-of-function mutations could be pharmacologically modulated in vitro using an existing FDA-approved drug, Nitazoxanide, suggesting a possible avenue for treatment, which is currently unavailable for ataxias.
| Type: | Article |
|---|---|
| Title: | Dominant Mutations in GRM1 Cause Spinocerebellar Ataxia Type 44 |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.ajhg.2017.08.005 |
| Publisher version: | http://doi.org/10.1016/j.ajhg.2017.08.005 |
| Language: | English |
| Additional information: | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| Keywords: | Homer, Purkinje cells, ataxia, atrophy, calcium, cerebellum, glutamate, intellectual disability, mGluR1, nitazoxanide |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Department of Neuromuscular Diseases UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1573229 |
Archive Staff Only
 |
View Item |
