A mutational hotspot in TUBB2A associated with impaired heterodimer formation and severe brain developmental disorders
Our findings expand the phenotypic and genotypic spectrum of <i>TUBB2A</i>-related disorders and identify Arg391 as a mutational hotspot linked to severe brain developmental disorders due to aberrant tubulin dynamics, highlighting the disruption of the <i>α</i>/<i>β</i>-tubulin heterodimer formation as the disease mechanism associated to this novel hotspot variant. These results provide new insights into disease mechanisms and offer a foundation for potential future therapeutic approaches aimed at stabilizing <i>α</i>/<i>β</i>-tubulin interactions.
Authors
- Gilad D. Evrony (ORCID: https://orcid.org/0000-0001-7621-2630)
- Miguel Angel Soler (ORCID: https://orcid.org/0000-0002-5780-9949)
- Andrea Accogli (ORCID: https://orcid.org/0000-0001-8724-6721)
- Gabriella Di Rosa (ORCID: https://orcid.org/0000-0003-3061-3249)
- Rosaria Nardello (ORCID: https://orcid.org/0000-0002-1041-6910)
- Jacopo Colella (ORCID: https://orcid.org/0000-0001-6595-8701)
- Valentina Turchetti
- Mathilde Nizon (ORCID: https://orcid.org/0000-0003-2170-4210)
- Benjamin Cognè
- Corrado Cecchetti
- Sara Fortuna (ORCID: https://orcid.org/0000-0002-8059-6064)
- Francesco Fabrizio Comisi (ORCID: https://orcid.org/0009-0002-8525-3041)
- Maurizio Delvecchio (ORCID: https://orcid.org/0000-0002-1528-0012)
- Mariasavina Severino (ORCID: https://orcid.org/0000-0003-4730-5322)
- Alessandro Vittori (ORCID: https://orcid.org/0000-0002-2377-3765)
- Giuseppe Di Pasquale (ORCID: https://orcid.org/0000-0002-5427-4504)
- C. Cataldo
- Giuseppe Donato Mangano (ORCID: https://orcid.org/0000-0001-6541-3170)
- Raffaele Falsaperla (ORCID: https://orcid.org/0000-0002-4482-3506)
- Piero Pavone (ORCID: https://orcid.org/0000-0002-5600-9560)
- Vincenzo Salpietro
- Alessandra Giliberti
- Emma Mizrahi-Powell
Institutions
- University of Messina (IT)
- University of Udine (IT)
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- University of Cagliari (IT)
- University of Ferrara (IT)
- Università degli Studi di Enna Kore (IT)
- University of L'Aquila (IT)
- Istituto Giannina Gaslini (IT)
- McGill University Health Centre (CA)
- Italian Institute of Technology (IT)
- University of Catania (IT)
- Center for Human Genetics (US)
- Bambino Gesù Children's Hospital (IT)
- Ospedale Microcitemico (IT)
- European Brain Research Institute (IT)
- Institut du Thorax (FR)
- National Hospital for Neurology and Neurosurgery (GB)
- Istituti di Ricovero e Cura a Carattere Scientifico (IT)
- Génétique Médicale & Génomique Fonctionelle (FR)
- University College London (GB)
- McGill University (CA)
- New York University (US)
- University of Palermo (IT)
- Nantes Université (FR)
Publication Details
- Journal
- Frontiers in Cellular Neuroscience
- Published
- 2025-09-25
- DOI
- https://doi.org/10.3389/fncel.2025.1664953
- Citations
- 1
- Primary Topic
- Microtubule and mitosis dynamics
- Type
- article
- Field-Weighted Citation Impact
- 1.15
Funders
- York University
- Ministero della Salute