biostudies-literatureMoreira DPConselho Nacional de Desenvolvimento Científico e TecnológicoCoordenação de Aperfeiçoamento de Pessoal de Nível SuperiorFundação de Amparo à Pesquisa do Estado de São Paulo803302https://www.ebi.ac.uk/biostudies/studies/S-EPMC8793280biostudies-literatureUnknown15Biallelic pathogenic variants in TBCK cause encephaloneuropathy, infantile hypotonia with psychomotor retardation, and characteristic facies 3 (IHPRF3). The molecular mechanisms underlying its neuronal phenotype are largely unexplored. In this study, we reported two sisters, who harbored biallelic variants in TBCK and met diagnostic criteria for IHPRF3. We provided evidence that TBCK may play an important role in the early secretory pathway in neuroprogenitor cells (iNPC) differentiated from induced pluripotent stem cells (iPSC). Lack of functional TBCK protein in iNPC is associated with impaired endoplasmic reticulum-to-Golgi vesicle transport and autophagosome biogenesis, as well as altered cell cycle progression and severe impairment in the capacity of migration. Alteration in these proFrontiers in cellular neuroscienceNeuroprogenitor Cells From Patients With TBCK Encephalopathy Suggest Deregulation of Early Secretory Vesicle Transport.PMC87932802013/08028-1466651/2014-7448536/2014-5Varella-Branco EFogo MLourenco NCVCardoso RRFerrari MFRde Lima MAGriesi-Oliveira KSertie ALKobayashi GSWeinmann KSMoreira DPPassos-Bueno MRMeneghetti MCZSilva ALTENader HBSuzuki AMZachi ECBertola DRfalseNeuroprogenitor Cells From Patients With TBCK Encephalopathy Suggest Deregulation of Early Secretory Vesicle Transport.Biallelic pathogenic variants in TBCK cause encephaloneuropathy, infantile hypotonia with psychomotor retardation, and characteristic facies 3 (IHPRF3). The molecular mechanisms underlying its neuronal phenotype are largely unexplored. In this study, we reported two sisters, who harbored biallelic variants in TBCK and met diagnostic criteria for IHPRF3. We provided evidence that TBCK may play an important role in the early secretory pathway in neuroprogenitor cells (iNPC) differentiated from induced pluripotent stem cells (iPSC). Lack of functional TBCK protein in iNPC is associated with impaired endoplasmic reticulum-to-Golgi vesicle transport and autophagosome biogenesis, as well as altered cell cycle progression and severe impairment in the capacity of migration. Alteration in these pro2021-01-01T00:00:00Z20212026-05-07T23:53:05.065Z2022-02-11T15:42:18.459ZS-EPMC87932803509542510.3389/fncel.2021.803302