Aberrant calcium channel splicing drives defects in cortical differentiation in Timothy syndrome

• Published in: eLife Vol. 8
• Main Authors: Panagiotakos, Georgia, Haveles, Christos, Arjun, Arpana, Petrova, Ralitsa, Rana, Anshul, Portmann, Thomas, Paşca, Sergiu P, Palmer, Theo D, Dolmetsch, Ricardo E
• Format: Journal Article
• Language: English
• Published: England eLife Science Publications, Ltd 23.12.2019; eLife Sciences Publications Ltd; eLife Sciences Publications, Ltd
• Subjects: Alternative splicing; Analysis; Autism; Brain; Calcium; calcium channel splicing; Calcium channels; Calcium channels (voltage-gated); Cell cycle; Cerebral cortex; Defects; Embryos; Gene expression; Gene mutation; human induced pluripotent stem cells; Inhibitory postsynaptic potentials; Mutants; Mutation; neuronal differentiation; Neurons; Neuroscience; Patients; Pluripotency; Point mutation; Schizophrenia; Stem cell transplantation; Stem cells; Stem Cells and Regenerative Medicine; Timothy syndrome; Canada; Iraq; human induced pluripotent stem cells; mouse; stem cells; neuroscience; regenerative medicine; calcium channel splicing; Timothy syndrome; human; neuronal differentiation

The syndromic autism spectrum disorder (ASD) Timothy syndrome (TS) is caused by a point mutation in the alternatively spliced exon 8A of the calcium channel Ca 1.2. Using mouse brain and human induced pluripotent stem cells (iPSCs), we provide evidence that the TS mutation prevents a normal developm...