MNX1 mutations causing neonatal diabetes: Review of the literature and report of a case with extra ‐pancreatic congenital defects presenting in severe diabetic ketoacidosis

We describe the genetic and clinical features of a preterm male infant with a homozygous [c.816C  >  A p.(Phe272Leu)]MNX1 mutation. Our proband is the first case to present in severe diabetic ketoacidosis (DKA), indicating severe insulin deficiency. Unlike the previously reported female case who had the same mutation and presented with isolated PNDM, our proband had hypospadias and congenital umbilical hernia and showed poor growth on follow up. Our case suggests thatMNX1 mutations causing NDM can result in a range of extra-pancreatic features and a variable phenotype, similar to other transcription factors causing NDM such asGATA6 andGATA4 mutations. We also cannot exclude the possibility of sex-biased expression ofMNX1 gene (which was recently reported for other monogenic/neonatal diabetes genes such as theNEUROD1 andHNF4A in humans) since the two male cases had associated multiple anomalies while the female case had isolated PNDM. Our report further defines the phenotype caused by recessive homozygousMNX1 mutations and explores potential new mechanisms regulatingMNX1 gene expression which should be further explored.
Source: Journal of Diabetes Investigation - Category: Endocrinology Authors: Tags: Mini Review Source Type: research