Permanent neonatal diabetes-causing insulin mutations have dominant negative effects on beta cell identity.

"Declaration of competing interest Authors declare no conflicts of interest."

"This research was supported by the 10.13039/100000041American Diabetes Association (grant #1-16-ICTS-029) and the NYSTEM IDEA award # C029552, Leona and Harry Helmsley Charitable Trust, Helmsley Trust Diabetes Cell Repository, the Juvenile Diabetes Research Foundation (JDRF), the Naomi Berrie Foundation program for Cellular Therapies of Diabetes, F.B. was supported by and the 10.13039/501100003196Italian Ministry of Health (project PE-2011-02350284). The contributions of P.A. and L.H. were supported by 10.13039/100000002NIH R01 DK48280. These studies used the resources of the Herbert Irving Comprehensive Cancer Center Flow Cytometry Shared Resources funded in part through Center Grant P30CA013696, and the Diabetes Research Center Flow Core Facility funded in part through DRC Center Grant (5P30DK063608) and the MBMG Core in the New York Nutrition and Obesity Research Center (5P30DK026687). YZ was supported by a China Scholarship Council PhD student fellowship. We thank Charles LeDuc for help with mouse studies, Rudolph Leibel for helpful input and critical reading of the manuscript, and Robin Goland for helpful discussions on beta cell replacement therapies. We appreciate Stefano Zucchini and Federica Ortolani for their clinical contributions to PTV1 and PTV2 patients."