Figure 1.

Location of INS promoter mutations

The top panel is a schematic of the human INS 5′ flanking sequence, showing approximate locations of established cis-regulatory sequences based on published mutational analyses of episomal sequences. The bottom panel shows a zoomed-in sequence that contains previously characterized MAFA, NEUROD1, and PDX1-bound cis-elements (C1, E1, and A1, respectively), as well as the CC element, with a graph that depicts the location of all INS promoter recessive mutations from our analysis. Each dot represents a patient, and the color represents the genotype. All single-base-pair mutations are located in the CC element, including a distinct 24-bp deletion that disrupts MAFA and NEUROD1 binding sites.