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

Keywords Diabetes.Genetics.HEX.HHEX.MODY.Monogenicdiabetes.Permanentneonataldiabetes.Persistenthyperinsulinaemichypoglycaemiaofinfancy.PHHI.PNDMAbbreviationsHEX haematopoietically expressed homeobox proteinHI hypoglycaemia of infancyHNF1α hepatocyte nuclear factor 1αPDX1 pancreatic and duodenal homeobox protein 1PNDM permanent neonatal diabetesTo the Editor: Haematopoietically expressed homeoboxprotein (HEX), a divergent homeobox transcription factor,is encoded by the HHEX gene and is required fororganogenesis of the ventral pancreas [1]. Mouse embryoslacking HHEX show a complete failure of ventral pancre-atic specification [1] and have deletions of the forebrain,midbrain and rostral hindbrain [2]. HEX functions fromvery early in embryogenesis (E4.5) through adulthood andis involved in the regulation of genes at multiple develop-mental states, including mature tissue and cell type [3].HHEX is expressed before the gene encoding the keypancreatic transcription factor, pancreatic and duodenalhomeobox protein 1 (PDX1), and mouse embryos lackingHHEX do not express PDX1 in the ventral pancreas,whereas expression in the dorsal pancreas is unaffected[1]. HEX has also been shown to activate hepatocytenuclear factor 1α (HNF1α), an important transcriptionfactor not only in beta cell development but also in theregulation of insulin secretion [4].Mutations in key transcription factors for pancreaticdevelopment are responsible for monogenic forms of betacell dysfunction, resulting in both hyper- and hypogly-caemia [5, 6]. Homozygous or compound heterozygousmutations in PDX1 cause permanent neonatal diabetes(PNDM) with pancreatic agenesis [5], whilst heterozygousmutations result in MODY [5]. Mutations in the genes