Title |
Dominant Mutations in GRM1 Cause Spinocerebellar Ataxia Type 44
|
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Published in |
American Journal of Human Genetics, September 2017
|
DOI | 10.1016/j.ajhg.2017.08.005 |
Pubmed ID | |
Authors |
Lauren M. Watson, Elizabeth Bamber, Ricardo Parolin Schnekenberg, Jonathan Williams, Conceição Bettencourt, Jennifer Lickiss, Sandeep Jayawant, Katherine Fawcett, Samuel Clokie, Yvonne Wallis, Penny Clouston, David Sims, Henry Houlden, Esther B.E. Becker, Andrea H. Németh |
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. |
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Geographical breakdown
Country | Count | As % |
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United Kingdom | 7 | 44% |
Argentina | 2 | 13% |
United States | 2 | 13% |
France | 1 | 6% |
Netherlands | 1 | 6% |
Brazil | 1 | 6% |
Unknown | 2 | 13% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 8 | 50% |
Scientists | 5 | 31% |
Practitioners (doctors, other healthcare professionals) | 3 | 19% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 82 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Ph. D. Student | 17 | 21% |
Student > Master | 11 | 13% |
Researcher | 11 | 13% |
Student > Postgraduate | 5 | 6% |
Student > Bachelor | 4 | 5% |
Other | 12 | 15% |
Unknown | 22 | 27% |
Readers by discipline | Count | As % |
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Medicine and Dentistry | 15 | 18% |
Biochemistry, Genetics and Molecular Biology | 14 | 17% |
Agricultural and Biological Sciences | 11 | 13% |
Neuroscience | 11 | 13% |
Chemistry | 2 | 2% |
Other | 4 | 5% |
Unknown | 25 | 30% |