Mutations in inhibitory GABAA receptor γ2 subunit gene, GABRG2, have been associated with genetic epilepsy syndromes including childhood absence epilepsy (CAE), pure febrile seizures (FS), generalized epilepsy with febrile seizures plus (GEFS+), and Dravet syndrome (DS). This dissertation elucidated the function of three epilepsy associated GABRG2 mutations, IVS6+2T->G, Q40X, and S443delC, which are found in both GABRG2 gene coding and non-coding regions. They impairing GABAA receptor biogenesis by multiple mechanisms including reducing subunit mRNA stability, impairing subunit folding, stability, or oligomerization and by inhibiting receptor trafficking. Aminoglycosides treatment could treat seizures induced by GABRG2(Q40X) mutation, but the treatment for epilepsies induced by other GABRG2 mutation is under investigation.
| Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-05072012-164429 |
| Date | 25 May 2012 |
| Creators | Tian, Mengnan |
| Contributors | Katherine Murray, Kevin Ess, Robert Macdonald, Ron Emeson, Douglas Mortlock |
| Publisher | VANDERBILT |
| Source Sets | Vanderbilt University Theses |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.vanderbilt.edu/available/etd-05072012-164429/ |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to Vanderbilt University or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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