Early neurological symptoms and epilepsy outcomes in individuals with the recurrent <scp> <i>GABRG2</i> </scp> p.( <scp>Ala106Thr</scp> ) gain‐of‐function variant: Structural and phenotypic insights
Although some individuals exhibited severe developmental impairment without epilepsy, our findings demonstrate that the recurrent GABRG2 p.(Ala106Thr) GoF variant is consistently associated with a severe neurodevelopmental phenotype. Despite its profound clinical impact, in silico tools consistently predict this variant as benign, highlighting a critical gap in current predictive models.
Authors
- Guido Rubboli (ORCID: https://orcid.org/0000-0002-5309-2514)
- Susan X. N. Lin (ORCID: https://orcid.org/0000-0003-3587-0957)
- Viviana Rizzo (ORCID: https://orcid.org/0009-0004-4289-0563)
- Francesca Bisulli (ORCID: https://orcid.org/0000-0002-1109-7296)
- Megan Yabumoto (ORCID: https://orcid.org/0000-0001-7569-9299)
- Elena Gardella (ORCID: https://orcid.org/0000-0002-7138-6022)
- Tommy Stödberg (ORCID: https://orcid.org/0000-0003-1242-5260)
- Reetta Kälviäinen (ORCID: https://orcid.org/0000-0003-2935-5131)
- Ali S. Kusay (ORCID: https://orcid.org/0000-0001-9123-9057)
- Sebastian Ortiz (ORCID: https://orcid.org/0000-0002-3432-1932)
- Lino Nobili (ORCID: https://orcid.org/0000-0001-9317-5405)
- Leena Jutila (ORCID: https://orcid.org/0000-0002-9600-4406)
- Tommaso Lo Barco (ORCID: https://orcid.org/0000-0002-3103-230X)
- Elisabetta Cesaroni (ORCID: https://orcid.org/0000-0002-7177-4500)
- Philip K. Ahring (ORCID: https://orcid.org/0000-0003-1807-3331)
- Katri Silvennoinen (ORCID: https://orcid.org/0000-0001-8456-0029)
- Sara I. Liin (ORCID: https://orcid.org/0000-0001-8493-0114)
- Federico Torta (ORCID: https://orcid.org/0000-0001-7545-7484)
- Rikke S. Møller (ORCID: https://orcid.org/0000-0002-9664-1448)
- Anni Saarela (ORCID: https://orcid.org/0000-0001-8582-2369)
- Laura Licchetta (ORCID: https://orcid.org/0000-0001-7979-9895)
- Rebekka S. Dahl (ORCID: https://orcid.org/0009-0003-2672-287X)
- Carla Marini (ORCID: https://orcid.org/0000-0002-9212-2691)
- Ghayda Mirzaa (ORCID: https://orcid.org/0000-0003-2648-7657)
- Elisa Fallica (ORCID: https://orcid.org/0009-0009-7071-343X)
- Felipe Castro‐Villablanca (ORCID: https://orcid.org/0000-0002-8569-6160)
- Alessandra Rossi (ORCID: https://orcid.org/0009-0005-4098-7844)
- Chiara Bagliani (ORCID: https://orcid.org/0009-0006-6782-8912)
- Christian Laugaard‐Jacobsen (ORCID: https://orcid.org/0000-0003-0003-4887)
Institutions
- Linköping University (SE)
- Universidad de Santiago de Chile (CL)
- University of Verona (IT)
- University of Copenhagen (DK)
- Seattle Children's Hospital (US)
- The University of Sydney (AU)
- Karolinska University Hospital (SE)
- University of Eastern Finland (FI)
- University of Southern Denmark (DK)
- University of Ferrara (IT)
- University of Washington (US)
- Alexander von Humboldt Biological Resources Research Institute (CO)
- Aalborg University Hospital (DK)
- Istituto Giannina Gaslini (IT)
- Karolinska Institutet (SE)
- UNSW Sydney (AU)
- Clínica Las Condes (CL)
- Azienda Ospedaliera Citta' della Salute e della Scienza di Torino (IT)
- Norcliffe Foundation (US)
- Kuopio University Hospital (FI)
- Istituto delle Scienze Neurologiche di Bologna (IT)
- Ospedale San Bassiano (IT)
- Epilepsy Action (GB)
- Epilepsy Foundation (AU)
- Ospedali Riuniti Umberto I (IT)
- Azienda Ospedaliera Carlo Poma (IT)
- University of Chile (CL)
- University of Genoa (IT)
- Aalborg University (DK)
- University of Bologna (IT)
Publication Details
- Journal
- Epilepsia
- Published
- 2025-12-06
- DOI
- https://doi.org/10.1111/epi.70045
- Primary Topic
- Genomics and Rare Diseases
- Type
- article
- Field-Weighted Citation Impact
- 0.00