Michele Iacomino, Nadia Houerbi, Sara Fortuna, Jennifer Howe, Shan Li, Giovanna Scorrano, Antonella Riva, Kai-Wen Cheng, Mandy Steiman, Iskra Peltekova, Afiqah Yusuf, Simona Baldassari, Serena Tamburro, Paolo Scudieri, Ilaria Musante, Armando Di Ludovico, Sara Guerrisi, Ganna Balagura, Antonio Corsello, Stephanie Efthymiou, David Murphy, Paolo Uva, Alberto Verrotti, Chiara Fiorillo, Maurizio Delvecchio, Andrea Accogli, Mayada Elsabbagh, Henry Houlden, Stephen W Scherer, Pasquale Striano, Federico Zara, Tsui-Fen Chou, Vincenzo Salpietro
The human PLAA gene encodes Phospholipase-A2-Activating-Protein (PLAA) involved in trafficking of membrane proteins. Through its PUL domain (PLAP, Ufd3p, and Lub1p), PLAA interacts with p97/VCP modulating synaptic vesicles recycling. Although few families carrying biallelic PLAA variants were reported with progressive neurodegeneration, consequences of monoallelic PLAA variants have not been elucidated. Using exome or genome sequencing we identified PLAA de-novo missense variants, affecting conserved residues within the PUL domain, in children affected with neurodevelopmental disorders (NDDs), including psychomotor regression, intellectual disability (ID) and autism spectrum disorders (ASDs)...
2024: Frontiers in Molecular Neuroscience