KPD is defined as a syndrome in which diabetes commences with ketoacidosis in individuals who are GAD and anti-islet cell antibody negative and have no known precipitating causes.
The importance of this transcription factor for adequate pancreatic islets functionality has been manifested by the association of mutations in <i>PAX4</i> with the development of diabetes, independently of its etiology.
Zinc deficiency was also associated with decreased expression of genes related to diabetes and pancreatic development in the embryo (Insa, Pax4, Pdx1).
In this study, we explored whether Pax4 gene transfer into α-cells could convert them into functional β-cells and thus provide therapeutic benefits for insulin-deficient diabetes.
R164W segregated with diabetes in the family of the proband and in vitro studies showed that it impairs the repressor activity of PAX4 on the insulin and glucagon promoters.