کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6021983 | 1580660 | 2014 | 11 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
A Novel GABRG2 mutation, p.R136*, in a family with GEFSÂ + and extended phenotypes
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کلمات کلیدی
CAEGGEPTCJMEGABRG2Premature translation termination codonGEFS +Electroencephalogram - الکتروانسفالوگرافیEpilepsy - بیماری صرعfebrile seizures - تب تشنجendoplasmic reticulum - شبکه آندوپلاسمی Childhood absence epilepsy - صرع فاقد دوران کودکیJuvenile myoclonic epilepsy - صرع مایوکلونیک نوجوانانReceptor trafficking - قاچاق گیرندهEEG - نوار مغزیGABAA receptors - گیرنده های GABAA
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
عصب شناسی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: A Novel GABRG2 mutation, p.R136*, in a family with GEFSÂ + and extended phenotypes A Novel GABRG2 mutation, p.R136*, in a family with GEFSÂ + and extended phenotypes](/preview/png/6021983.png)
چکیده انگلیسی
Genetic mutations in voltage-gated and ligand-gated ion channel genes have been identified in a small number of Mendelian families with genetic generalised epilepsies (GGEs). They are commonly associated with febrile seizures (FS), childhood absence epilepsy (CAE) and particularly with generalised or genetic epilepsy with febrile seizures plus (GEFS +). In clinical practice, despite efforts to categorise epilepsy and epilepsy families into syndromic diagnoses, many generalised epilepsies remain unclassified with a presumed genetic basis. During the systematic collection of epilepsy families, we assembled a cohort of families with evidence of GEFS + and screened for variations in the γ2 subunit of the γ-aminobutyric acid (GABA) type A receptor gene (GABRG2). We detected a novel GABRG2(p.R136*) premature translation termination codon in one index-case from a two-generation nuclear family, presenting with an unclassified GGE, a borderline GEFS + phenotype with learning difficulties and extended behavioural presentation. The GABRG2(p.R136*) mutation segregates with the febrile seizure component of this family's GGE and is absent in 190 healthy control samples. In vitro expression assays demonstrated that γ2(p.R136*) subunits were produced, but had reduced cell-surface and total expression. When γ2(p.R136*) subunits were co-expressed with α1 and β2 subunits in HEK 293T cells, GABA-evoked currents were reduced. Furthermore, γ2(p.R136*) subunits were highly-expressed in intracellular aggregations surrounding the nucleus and endoplasmic reticulum (ER), suggesting compromised receptor trafficking. A novel GABRG2(p.R136*) mutation extends the spectrum of GABRG2 mutations identified in GEFS + and GGE phenotypes, causes GABAA receptor dysfunction, and represents a putative epilepsy mechanism.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurobiology of Disease - Volume 64, April 2014, Pages 131-141
Journal: Neurobiology of Disease - Volume 64, April 2014, Pages 131-141
نویسندگان
Ann J. Johnston, Jing-Qiong Kang, Wangzhen Shen, William O. Pickrell, Thomas D. Cushion, Jeffrey S. Davies, Kristin Baer, Jonathan G.L. Mullins, Carrie L. Hammond, Seo-Kyung Chung, Rhys H. Thomas, Cathy White, Phil E.M. Smith, Robert L. Macdonald,