PDX-1 related diabetes: a case series of two families highlighting challenges in MODY diagnosis.

PDX1-MODY is a rare, dominantly inherited form of monogenic diabetes resulting from pathogenic variants in the PDX1 (IPF1) gene. It typically presents with early-onset, non-ketotic hyperglycemia and variable insulin dependence. This report describes two unrelated families carrying confirmed PDX1 variants (c.313G > T [p.Glu105*] and c.492G > T [p.Glu164Asp]) that illustrate the clinical and genetic heterogeneity of PDX1-MODY. Comprehensive next-generation sequencing (NGS) including a 36-gene panel for monogenic diabetes confirmed the variants, which were classified according to ACMG/AMP 2015 guidelines as "pathogenic" (p.Glu105)* and "likely pathogenic" (p.Glu164Asp). Clinically, both pedigrees exhibited preserved C-peptide secretion over decades, absence of autoimmune markers, and progressive β-cell dysfunction, confirming the variable but characteristic phenotype of PDX1-MODY. These cases expand the mutational and phenotypic spectrum of PDX1-MODY and highlight the importance of considering monogenic diabetes in early-onset, antibody-negative cases.