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You searched for subject:(GABRG2). Showing records 1 – 3 of 3 total matches.

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Vanderbilt University

1. Tian, Mengnan. Functional characterization of epilepsy associated GABRG2 mutations.

Degree: PhD, Pharmacology, 2012, Vanderbilt University

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. Advisors/Committee Members: Katherine Murray (committee member), Kevin Ess (committee member), Douglas Mortlock (committee member), Robert Macdonald (Committee Chair), Ron Emeson (Committee Chair).

Subjects/Keywords: trafficking; GABAA receptor; GABRG2; epilepsy

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Tian, M. (2012). Functional characterization of epilepsy associated GABRG2 mutations. (Doctoral Dissertation). Vanderbilt University. Retrieved from http://hdl.handle.net/1803/12274

Chicago Manual of Style (16th Edition):

Tian, Mengnan. “Functional characterization of epilepsy associated GABRG2 mutations.” 2012. Doctoral Dissertation, Vanderbilt University. Accessed January 16, 2021. http://hdl.handle.net/1803/12274.

MLA Handbook (7th Edition):

Tian, Mengnan. “Functional characterization of epilepsy associated GABRG2 mutations.” 2012. Web. 16 Jan 2021.

Vancouver:

Tian M. Functional characterization of epilepsy associated GABRG2 mutations. [Internet] [Doctoral dissertation]. Vanderbilt University; 2012. [cited 2021 Jan 16]. Available from: http://hdl.handle.net/1803/12274.

Council of Science Editors:

Tian M. Functional characterization of epilepsy associated GABRG2 mutations. [Doctoral Dissertation]. Vanderbilt University; 2012. Available from: http://hdl.handle.net/1803/12274

2. Gradišnik, Peter. Vloga polimorfizma v genu GABRG2 in insercije citozina v genu SEZ6 ter kliničnih dejavnikov pri nastanku vročinskih krčev.

Degree: 2016, Univerza v Mariboru

NAMEN. Vročinski krči so najpogostejša konvulzivna motnja v otroštvu. Na njihov nastanek vplivajo tako genetski kot okoljski dejavniki. Kandidatne gene predstavljajo predvsem geni, ki kodirajo sestavo enot napetostno-odvisnih ionskih kanalčkov, receptorjev v centralnem živčevju ter geni, ki vplivajo na medsebojno prepoznavo živčnih celic in njihovo povezovanje. Naš namen je bil, prispevati drobec informacije k raziskavam tako na kliničnem kot na genetskem področju. Na slednjem smo se posvetili raziskavi vloge genov SEZ6 in GABRG2, ki bi bila lahko, glede na rezultate predhodnih študij, vpletena v nastanek vročinskih krčev, pa tudi kasnejše epilepsije. METODE. V prospektivno študijo smo vključili 179 otrok, obravnavanih na Kliniki za pediatrijo Maribor zaradi prve epizode vročinskih krčev. Iz obstoječe medicinske dokumentacije in kasnejšim dopolnjevanjem anamneze smo pridobili podatke o kliničnih parametrih. EEG posnetke smo opravili pri bolnikih brez povišane temperature 2 do 3 tedne po napadu. Paciente smo klinično sledili 2,1 do 9,2 let, v povprečju 6,6 let. Ob tem nas je zanimalo število ponovitev vročinskih krčev in morebiten prehod v epilepsijo. Iz vzorcev njihove krvi in iz vzorcev krvi 200 zdravih odraslih preiskovancev kontrolne skupine smo izolirali genomsko DNA ter ugotavljali prisotnost polimorfizma rs209354 v genu GABRG2 in polimorfizma rs11450637 (insercije citozina) v genu SEZ6 z metodo polimerazne verižne reakcije, agarozne gelske in kapilarne elektroforeze. Kategorične spremenljivke smo primerjali s testom hi-kvadrat ali Fischerjevim testom. Za normalno razporejene zvezne spremenljivke smo uporabili Studentov test t, Mann-Whitneyev test U pa smo uporabili, kadar razporeditev ni bila normalna. Za primerne spremenljivke smo uporabili tudi model binarne regresije. REZULTATI. Vročinski krči so se vsaj enkrat ponovili pri 58 (32,5 %) otrok. Pri 32 otrocih (17,9 %) je šlo za le eno ponovitev, večkratne ponovitve je imelo 26 (14,5 %) otrok. Epileptiformne spremembe smo našli pri 30 otrocih (16,8 %). Med njimi je polovica imela primarno generalizirane, polovica pa žariščne spremembe. Do razvoja epilepsije je prišlo pri 12 (6,7 %) otrok. Med 27 bolniki, pri katerih je bil prvi napad klinično žariščen, je 5 otrok (18,5 %) kasneje zbolelo za epilepsijo. Ob hkratni vključitvi klinične žariščnosti in žariščnih epileptiformnih sprememb je do razvoja epilepsije prišlo v polovici primerov. Z višjim tveganjem nastanka epilepsije so povezani tudi nizko povišana temperatura ob prvi epizodi vročinskih krčev, število ponovitev vročinskih krčev in pozitivna družinska anamneza epilepsije. Dejavniki tveganja ponovitev vročinskih krčev so pozitivna družinska anamneza vročinskih krčev, nizka starost ob prvi epizodi, ponovitev napada v roku 24 ur, pa tudi žariščne spremembe v EEG. Z višjo verjetnostjo prve ponovitve nista pomembno povezana klinična žariščnost napada in nizka temperatura ob prvi epizodi, vendar obstaja statistično značilna obratno sorazmerna povezava višine telesne temperature in števila ponovitev. Polimorfizem… Advisors/Committee Members: Marčun Varda, Nataša.

Subjects/Keywords: vročinski krči; epilepsija; otrok; EEG; genetika; SEZ6; GABRG2; febrile seizures; epilepsy; child; EEG; genetics; SEZ6; GABRG2

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Gradišnik, P. (2016). Vloga polimorfizma v genu GABRG2 in insercije citozina v genu SEZ6 ter kliničnih dejavnikov pri nastanku vročinskih krčev. (Doctoral Dissertation). Univerza v Mariboru. Retrieved from https://dk.um.si/IzpisGradiva.php?id=57035 ; https://dk.um.si/Dokument.php?id=88679&dn= ; https://plus.si.cobiss.net/opac7/bib/5688895?lang=sl

Chicago Manual of Style (16th Edition):

Gradišnik, Peter. “Vloga polimorfizma v genu GABRG2 in insercije citozina v genu SEZ6 ter kliničnih dejavnikov pri nastanku vročinskih krčev.” 2016. Doctoral Dissertation, Univerza v Mariboru. Accessed January 16, 2021. https://dk.um.si/IzpisGradiva.php?id=57035 ; https://dk.um.si/Dokument.php?id=88679&dn= ; https://plus.si.cobiss.net/opac7/bib/5688895?lang=sl.

MLA Handbook (7th Edition):

Gradišnik, Peter. “Vloga polimorfizma v genu GABRG2 in insercije citozina v genu SEZ6 ter kliničnih dejavnikov pri nastanku vročinskih krčev.” 2016. Web. 16 Jan 2021.

Vancouver:

Gradišnik P. Vloga polimorfizma v genu GABRG2 in insercije citozina v genu SEZ6 ter kliničnih dejavnikov pri nastanku vročinskih krčev. [Internet] [Doctoral dissertation]. Univerza v Mariboru; 2016. [cited 2021 Jan 16]. Available from: https://dk.um.si/IzpisGradiva.php?id=57035 ; https://dk.um.si/Dokument.php?id=88679&dn= ; https://plus.si.cobiss.net/opac7/bib/5688895?lang=sl.

Council of Science Editors:

Gradišnik P. Vloga polimorfizma v genu GABRG2 in insercije citozina v genu SEZ6 ter kliničnih dejavnikov pri nastanku vročinskih krčev. [Doctoral Dissertation]. Univerza v Mariboru; 2016. Available from: https://dk.um.si/IzpisGradiva.php?id=57035 ; https://dk.um.si/Dokument.php?id=88679&dn= ; https://plus.si.cobiss.net/opac7/bib/5688895?lang=sl


Vanderbilt University

3. Huang, Xuan. Epilepsy-associated mutations in GABRG2: characterization and therapeutic opportunities.

Degree: PhD, Neuroscience, 2014, Vanderbilt University

Epilepsy is a neurological disorder affecting almost one percent of the population, and genetic epilepsy are those caused by a presumed or unknown genetic factor(s). Mutations in GABAA receptors, pentameric chloride ion channels mediating fast inhibitory neurotransmission, have been identified in patients and families with epilepsy and found to cause epilepsy in animal models. The majority of synaptic GABAARs are αβγ type receptors composed of two α, two β and one γ2 subunits, and half of these epilepsy-associated GABAAR mutations are located in γ2 subunits encoded by the GABRG2 gene. A better understanding of how different types of epilepsy-associated GABRG2 mutations affect receptor trafficking and channel function, and how these mutations cause epilepsy in mouse models, will facilitate future epilepsy diagnosis as well as treatments. Here we have studied three different types of mutations represented by GABRG2(N79S, R82Q, and P83S), GABRG2(Q40X), and GABRG2(Q390X), in cultured HEK cells or animal models. We found that missense mutations located in receptor interface will disrupt receptor assembly and trafficking, which may be improved by slowing receptor biogenesis. We found that nonsense mutations showing loss of function could be partially rescued using gentamicin-induced stop codon read-through. Finally we showed that gene-target therapy could reverse the seizure phenotype in a mouse model carrying a detrimental mutation with dominant negative effects. To conclude, we have shown different molecular mechanisms are associated with these mutations, and distinct mutation-specific therapy may be potentially developed for future treatments. Advisors/Committee Members: Richard M. Breyer (committee member), Kevin C. Ess (committee member), Robert L. Macdonald (committee member), Alfred L. George (Committee Chair), Bruce D. Carter (Committee Chair).

Subjects/Keywords: GABA(A) receptors; GABRG2; genetic epilepsy; mutation; therapy

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Huang, X. (2014). Epilepsy-associated mutations in GABRG2: characterization and therapeutic opportunities. (Doctoral Dissertation). Vanderbilt University. Retrieved from http://hdl.handle.net/1803/14755

Chicago Manual of Style (16th Edition):

Huang, Xuan. “Epilepsy-associated mutations in GABRG2: characterization and therapeutic opportunities.” 2014. Doctoral Dissertation, Vanderbilt University. Accessed January 16, 2021. http://hdl.handle.net/1803/14755.

MLA Handbook (7th Edition):

Huang, Xuan. “Epilepsy-associated mutations in GABRG2: characterization and therapeutic opportunities.” 2014. Web. 16 Jan 2021.

Vancouver:

Huang X. Epilepsy-associated mutations in GABRG2: characterization and therapeutic opportunities. [Internet] [Doctoral dissertation]. Vanderbilt University; 2014. [cited 2021 Jan 16]. Available from: http://hdl.handle.net/1803/14755.

Council of Science Editors:

Huang X. Epilepsy-associated mutations in GABRG2: characterization and therapeutic opportunities. [Doctoral Dissertation]. Vanderbilt University; 2014. Available from: http://hdl.handle.net/1803/14755

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