Annalisa Vetro, Cristiana Pelorosso, Simona Balestrini, Alessio Masi, Sophie Hambleton, Emanuela Argilli, Valerio Conti, Simone Giubbolini, Rebekah Barrick, Gaber Bergant, Karin Writzl, Emilia K Bijlsma, Theresa Brunet, Pilar Cacheiro, Davide Mei, Anita Devlin, Mariëtte J V Hoffer, Keren Machol, Guido Mannaioni, Masamune Sakamoto, Manoj P Menezes, Thomas Courtin, Elliott Sherr, Riccardo Parra, Ruth Richardson, Tony Roscioli, Marcello Scala, Celina von Stülpnagel, Damian Smedley, Annalaura Torella, Jun Tohyama, Reiko Koichihara, Keisuke Hamada, Kazuhiro Ogata, Takashi Suzuki, Atsushi Sugie, Jasper J van der Smagt, Koen van Gassen, Stephanie Valence, Emma Vittery, Stephen Malone, Mitsuhiro Kato, Naomichi Matsumoto, Gian Michele Ratto, Renzo Guerrini
By converting physical forces into electrical signals or triggering intracellular cascades, stretch-activated ion channels allow the cell to respond to osmotic and mechanical stress. Knowledge of the pathophysiological mechanisms underlying associations of stretch-activated ion channels with human disease is limited. Here, we describe 17 unrelated individuals with severe early-onset developmental and epileptic encephalopathy (DEE), intellectual disability, and severe motor and cortical visual impairment associated with progressive neurodegenerative brain changes carrying ten distinct heterozygous variants of TMEM63B, encoding for a highly conserved stretch-activated ion channel...
August 3, 2023: American Journal of Human Genetics