Generation of three human induced pluripotent stem cell lines from FGFR2-linked syndromic craniosynostosis patients

Craniosynostosis is a multigenic congenital condition in which one or more calvarial sutures have prematurely fused during the development of the fetus. Mutation in FGFR2 are associated with the development of syndromic craniosynostosis, such as Crouzon, Apert, and Pfeifer Syndrome. Investigation of FGFR2-linked craniosynostosis is hindered by the lack of appropriate in vitro models. Patient-derived human induced pluripotent stem cell (hiPSC) in vitro disease models provide the opportunity to investigate the disease, identify molecular targets for pharmaceutical treatments, and enable the generation of autologous pluripotent stem cell catalogues. Here, we report three patient-derived hiPSC lines carrying the FGFR2 mutation C342Y, S252W, or E565G, respectively. The patient hiPSC lines express characteristic pluripotency markers, and display distinct phosphorylation profiles under unstimulated conditions. The FGFR2C342Y shows autophosphorylation in the absence of bFGF ligand, although downstream docking proteins PLCγ and FRS2α are not phosphorylated. FGFR2S252W and FGFR2E565G hiPSCs possess increased phosphorylation of docking proteins PLCγ and FRS2α while FGFR2 is not phosphorylated. These patient hiPSC lines provide molecular and cellular options to investigate FGFR2-linked craniosynostosis in the patient-specific genomic context and develop therapeutic modalities.