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Maternal transmission of a rare GABRB3 signal peptide variant is associated with autism.
Delahanty, R J; Kang, J Q; Brune, C W; Kistner, E O; Courchesne, E; Cox, N J; Cook, E H; Macdonald, R L; Sutcliffe, J S.
Afiliação
  • Delahanty RJ; Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN 37232-8548, USA.
Mol Psychiatry ; 16(1): 86-96, 2011 Jan.
Article em En | MEDLINE | ID: mdl-19935738
Maternal 15q11-q13 duplication is the most common copy number variant in autism, accounting for ∼1-3% of cases. The 15q11-q13 region is subject to epigenetic regulation, and genomic copy number losses and gains cause genomic disorders in a parent-of-origin-specific manner. One 15q11-q13 locus encodes the GABA(A) receptor ß3 subunit gene (GABRB3), which has been implicated by several studies in both autism and absence epilepsy, and the co-morbidity of epilepsy in autism is well established. We report that maternal transmission of a GABRB3 signal peptide variant (P11S), previously implicated in childhood absence epilepsy, is associated with autism. An analysis of wild-type and mutant ß3 subunit-containing α1ß3γ2 or α3ß3γ2 GABA(A) receptors shows reduced whole-cell current and decreased ß3 subunit protein on the cell surface due to impaired intracellular ß3 subunit processing. We thus provide the first evidence of an association between a specific GABA(A) receptor defect and autism, direct evidence that this defect causes synaptic dysfunction that is autism relevant and the first maternal risk effect in the 15q11-q13 autism duplication region that is linked to a coding variant.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Transtorno Autístico / Cromossomos Humanos Par 15 / Receptores de GABA-A Tipo de estudo: Risk_factors_studies Limite: Female / Humans / Male Idioma: En Revista: Mol Psychiatry Assunto da revista: BIOLOGIA MOLECULAR / PSIQUIATRIA Ano de publicação: 2011 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Transtorno Autístico / Cromossomos Humanos Par 15 / Receptores de GABA-A Tipo de estudo: Risk_factors_studies Limite: Female / Humans / Male Idioma: En Revista: Mol Psychiatry Assunto da revista: BIOLOGIA MOLECULAR / PSIQUIATRIA Ano de publicação: 2011 Tipo de documento: Article País de afiliação: Estados Unidos