Andreas Hentschel, Nancy Meyer, Nicolai Kohlschmidt, Claudia Groß, Albert Sickmann, Ulrike Schara-Schmidt, Fabian Förster, Ana Töpf, Jon Christiansen, Rita Horvath, Matthias Vorgerd, Rachel Thompson, Kiran Polaparapu, Hanns Lochmüller, Corinna Preusse, Luis Hannappel, Anne Schänzer, Anika Grüneboom, Andrea Gangfuß, Andreas Roos
PPP1R21 acts as a co-factor for protein phosphatase 1 (PP1), an important serine/threonine phosphatase known to be essential for cell division, control of glycogen metabolism, protein synthesis, and muscle contractility. Bi-allelic pathogenic variants in PPP1R21 were linked to a neurodevelopmental disorder with hypotonia, facial dysmorphism, and brain abnormalities (NEDHFBA) with pediatric onset. Functional studies unraveled impaired vesicular transport as being part of PPP1R21-related pathomechanism. To decipher further the pathophysiological processes leading to the clinical manifestation of NEDHFBA, we investigated the proteomic signature of fibroblasts derived from the first NEDHFBA patient harboring a splice-site mutation in PPP1R21 and presenting with a milder phenotype...
January 24, 2023: Molecular Neurobiology