A novel hypomorphic PDX1 mutation responsible for permanent neonatal diabetes with subclinical exocrine deficiency. Diabetes. 2010; 59:733–740. [PubMed: 20009086] Scott et al. Page 26 Nat Genet. Author manuscript; available

OBJECTIVE—Genes responsible for monogenic forms of dia-betes have proven very valuable for understanding key mecha-nisms involved in -cell development and function. Genetic study of selected families is a powerful strategy to identify such genes. We studied a consanguineous family with two first cousins affected by neonatal diabetes; their four parents had a common ancestor, suggestive of a fully penetrant recessive mutation. RESEARCH DESIGN AND METHODS—We performed ge-netic studies of the family, detailed clinical and biochemical investigations of the patients and the four parents, and biochem-ical and functional studies of the new mutation. RESULTS—We found a novel mutation in the pancreatic and duodenal homeobox 1 gene (PDX1, IPF1) in the two patients, which segregated with diabetes in the homozygous state. The mutation resulted in an E178G substitution in the PDX1 home