The
MNX1
gene encodes a homeobox transcription factor found to be important for pancreatic beta cell differentiation and development. Mutations of the
MNX1
gene that cause permanent neonatal diabetes mellitus (PNDM) are rare and have been reported in only two cases. Both cases presented with hyperglycemia, with one case having isolated PNDM while the other had PNDM and multiple neurologic, skeletal, lung, and urologic congenital anomalies resulting in death in early infancy. 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 that
MNX1
mutations causing NDM can result in a range of extra‐pancreatic features and a variable phenotype, similar to other transcription factors causing NDM such as
GATA6
and
GATA4
mutations. We also cannot exclude the possibility of sex‐biased expression of
MNX1
gene (which was recently reported for other monogenic/neonatal diabetes genes such as the
NEUROD1
and
HNF4A
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 homozygous
MNX1
mutations and explores potential new mechanisms regulating
MNX1
gene expression which should be further explored.