Figure 1.

Identification of homozygous MANF mutation in two patients with childhood diabetes. A: Pedigrees of the two case subjects with homozygous MANF variants. Square symbolizes male, and circle symbolizes female. Black-shaded area indicates the presence of diabetes; blue and red areas indicate the presence of short stature and deafness, respectively, whereas the gray-shaded area indicates the presence of microcephaly and developmental delay. B: Schematic presentation of the MANF gene KO strategy using CRISPR/Cas9. The positions of patient mutations are marked with red arrows, and the guides used to delete exon 1 are presented as blue arrowheads. C: Representative immunoblot showing the absence of the MANF protein in the generated clone. α-Tubulin was used as a loading control.