Homozygous RFX6 mutations cause Mitchell-Riley syndrome associated with PNDM.47 RFX6 plays a crucial role during pancreatic development in regulating the differentiation of pancreatic progenitors into endocrine cells48,49 and in maintaining β-cell function.50,51 In line with this, RFX6−/− hESCs generated a reduced population of pancreatic progenitors (~ 40% decrease in the PDX1+ cells) and lacked INS+ and GCG+ endocrine cells.20 Therefore, RFX6 mutations cause PNDM due to aberrant development of the pancreatic progenitors and endocrine lineages. Here, RFX6 is linked to Hypoplastic pancreas-intestinal atresia-hypoplastic gallbladder syndrome.