Homozygous Mutations in NEUROD1 Are Responsible for a Novel Syndrome of Permanent Neonatal Diabetes and Neurological Abnormalities

OBJECTIVE—NEUROD1 is expressed in both developing and mature -cells. Studies in mice suggest that this basic helix-loop-helix transcription factor is critical in the development of endo-crine cell lineage. Heterozygous mutations have previously been identified as a rare cause of maturity-onset diabetes of the young (MODY). We aimed to explore the potential contribution of NEUROD1 mutations in patients with permanent neonatal diabetes. RESEARCH DESIGN AND METHODS—We sequenced the NEUROD1 gene in 44 unrelated patients with permanent neona-tal diabetes of unknown genetic etiology. RESULTS—Two homozygous mutations in NEUROD1 (c.427_ 428del and c.364dupG) were identified in two patients. Both mutations introduced a frameshift that would be predicted to generate a truncated protein completely lacking the activatin