Mutations in HHEX are not a common cause of monogenic forms of beta cell dysfunction

Excerpt

Haematopoietically expressed homeobox protein (HEX), a divergent homeobox transcription factor, is encoded by the HHEX gene and is required for organogenesis of the ventral pancreas [1]. Mouse embryos lacking HHEX show a complete failure of ventral pancreatic specification [1] and have deletions of the forebrain, midbrain and rostral hindbrain [2]. HEX functions from very early in embryogenesis (E4.5) through adulthood and is involved in the regulation of genes at multiple developmental states, including mature tissue and cell type [3]. HHEX is expressed before the gene encoding the key pancreatic transcription factor, pancreatic and duodenal homeobox protein 1 (PDX1), and mouse embryos lacking HHEX do not express PDX1 in the ventral pancreas, whereas expression in the dorsal pancreas is unaffected [1]. HEX has also been shown to activate hepatocyte nuclear factor 1α (HNF1α), an important transcription factor not only in beta cell development but also in the regulation of insulin secretion [4]. …