Structural mapping of GABRB3 variants ...
Type de document :
Article dans une revue scientifique: Article original
PMID :
URL permanente :
Titre :
Structural mapping of GABRB3 variants reveals genotype-phenotype correlations
Auteur(s) :
Johannesen, K. M. [Auteur]
University of Southern Denmark [SDU]
Iqbal, S. [Auteur]
Guazzi, M. [Auteur]
Mohammadi, N. A. [Auteur]
Perez-Palma, E. [Auteur]
Schaefer, E. [Auteur]
De Saint Martin, A. [Auteur]
Abiwarde, M. T. [Auteur]
Mctague, A. [Auteur]
Pons, R. [Auteur]
Piton, A. [Auteur]
Kurian, M. A. [Auteur]
Ambegaonkar, G. [Auteur]
Firth, H. [Auteur]
Sanchis-Juan, A. [Auteur]
Deprez, M. [Auteur]
Jansen, K. [Auteur]
De Waele, L. [Auteur]
Briltra, E. H. [Auteur]
Verbeek, N. E. [Auteur]
Van Kempen, M. [Auteur]
Fazeli, W. [Auteur]
Striano, P. [Auteur]
Zara, F. [Auteur]
Visser, G. [Auteur]
Braakman, H. M. H. [Auteur]
Haeusler, M. [Auteur]
Elbracht, M. [Auteur]
Vaher, U. [Auteur]
Smol, Thomas [Auteur]
Maladies Rares du Développement : Génétique, Régulation et Protéomique (RADEME) - ULR 7364
Lemke, J. R. [Auteur]
Platzer, K. [Auteur]
Kennedy, J. [Auteur]
Klein, K. M. [Auteur]
Au, P. Y. B. [Auteur]
Smyth, K. [Auteur]
Kaplan, J. [Auteur]
Thomas, M. [Auteur]
Dewenter, M. K. [Auteur]
Dinopoulos, A. [Auteur]
Campbell, A. J. [Auteur]
Lal, D. [Auteur]
Lederer, D. [Auteur]
Liao, V. W. Y. [Auteur]
Ahring, P. K. [Auteur]
Moller, R. S. [Auteur]
Gardella, E. [Auteur]
University of Southern Denmark [SDU]
University of Southern Denmark [SDU]
Iqbal, S. [Auteur]
Guazzi, M. [Auteur]
Mohammadi, N. A. [Auteur]
Perez-Palma, E. [Auteur]
Schaefer, E. [Auteur]
De Saint Martin, A. [Auteur]
Abiwarde, M. T. [Auteur]
Mctague, A. [Auteur]
Pons, R. [Auteur]
Piton, A. [Auteur]
Kurian, M. A. [Auteur]
Ambegaonkar, G. [Auteur]
Firth, H. [Auteur]
Sanchis-Juan, A. [Auteur]
Deprez, M. [Auteur]
Jansen, K. [Auteur]
De Waele, L. [Auteur]
Briltra, E. H. [Auteur]
Verbeek, N. E. [Auteur]
Van Kempen, M. [Auteur]
Fazeli, W. [Auteur]
Striano, P. [Auteur]
Zara, F. [Auteur]
Visser, G. [Auteur]
Braakman, H. M. H. [Auteur]
Haeusler, M. [Auteur]
Elbracht, M. [Auteur]
Vaher, U. [Auteur]
Smol, Thomas [Auteur]
![refId](/themes/Mirage2//images/idref.png)
Maladies Rares du Développement : Génétique, Régulation et Protéomique (RADEME) - ULR 7364
Lemke, J. R. [Auteur]
Platzer, K. [Auteur]
Kennedy, J. [Auteur]
Klein, K. M. [Auteur]
Au, P. Y. B. [Auteur]
Smyth, K. [Auteur]
Kaplan, J. [Auteur]
Thomas, M. [Auteur]
Dewenter, M. K. [Auteur]
Dinopoulos, A. [Auteur]
Campbell, A. J. [Auteur]
Lal, D. [Auteur]
Lederer, D. [Auteur]
Liao, V. W. Y. [Auteur]
Ahring, P. K. [Auteur]
Moller, R. S. [Auteur]
Gardella, E. [Auteur]
University of Southern Denmark [SDU]
Titre de la revue :
Genetics in Medicine
Nom court de la revue :
Genet. Med.
Numéro :
24
Pagination :
681-693
Date de publication :
2023-09-06
ISSN :
1098-3600
Mot(s)-clé(s) en anglais :
Epilepsy
GABA
GABRB3
Genetics
Mapping
GABA
GABRB3
Genetics
Mapping
Discipline(s) HAL :
Sciences du Vivant [q-bio]
Résumé en anglais : [en]
Purpose
Pathogenic variants in GABRB3 have been associated with a spectrum of phenotypes from severe developmental disorders and epileptic encephalopathies to milder epilepsy syndromes and mild intellectual disability ...
Lire la suite >Purpose Pathogenic variants in GABRB3 have been associated with a spectrum of phenotypes from severe developmental disorders and epileptic encephalopathies to milder epilepsy syndromes and mild intellectual disability (ID). In this study, we analyzed a large cohort of individuals with GABRB3 variants to deepen the phenotypic understanding and investigate genotype–phenotype correlations. Methods Through an international collaboration, we analyzed electro-clinical data of unpublished individuals with variants in GABRB3, and we reviewed previously published cases. All missense variants were mapped onto the 3-dimensional structure of the GABRB3 subunit, and clinical phenotypes associated with the different key structural domains were investigated. Results We characterized 71 individuals with GABRB3 variants, including 22 novel subjects, expressing a wide spectrum of phenotypes. Interestingly, phenotypes correlated with structural locations of the variants. Generalized epilepsy, with a median age at onset of 12 months, and mild-to-moderate ID were associated with variants in the extracellular domain. Focal epilepsy with earlier onset (median: age 4 months) and severe ID were associated with variants in both the pore-lining helical transmembrane domain and the extracellular domain. Conclusion These genotype–phenotype correlations will aid the genetic counseling and treatment of individuals affected by GABRB3-related disorders. Future studies may reveal whether functional differences underlie the phenotypic differences.Lire moins >
Lire la suite >Purpose Pathogenic variants in GABRB3 have been associated with a spectrum of phenotypes from severe developmental disorders and epileptic encephalopathies to milder epilepsy syndromes and mild intellectual disability (ID). In this study, we analyzed a large cohort of individuals with GABRB3 variants to deepen the phenotypic understanding and investigate genotype–phenotype correlations. Methods Through an international collaboration, we analyzed electro-clinical data of unpublished individuals with variants in GABRB3, and we reviewed previously published cases. All missense variants were mapped onto the 3-dimensional structure of the GABRB3 subunit, and clinical phenotypes associated with the different key structural domains were investigated. Results We characterized 71 individuals with GABRB3 variants, including 22 novel subjects, expressing a wide spectrum of phenotypes. Interestingly, phenotypes correlated with structural locations of the variants. Generalized epilepsy, with a median age at onset of 12 months, and mild-to-moderate ID were associated with variants in the extracellular domain. Focal epilepsy with earlier onset (median: age 4 months) and severe ID were associated with variants in both the pore-lining helical transmembrane domain and the extracellular domain. Conclusion These genotype–phenotype correlations will aid the genetic counseling and treatment of individuals affected by GABRB3-related disorders. Future studies may reveal whether functional differences underlie the phenotypic differences.Lire moins >
Langue :
Anglais
Audience :
Internationale
Vulgarisation :
Non
Établissement(s) :
Université de Lille
CHU Lille
CHU Lille
Collections :
Date de dépôt :
2024-05-15T22:09:01Z
2024-06-19T10:25:24Z
2024-06-19T10:25:24Z