Systematic analysis of loss-of-function variants across MODY genes demonstrates gene-specific effects and expands the spectrum of INS variants causing MODY

Key Points

• The research aims to evaluate the pathogenic effects of loss-of-function variants in MODY genes, focusing on their implications for diagnosis.
• Systematic analysis of loss-of-function variants across multiple MODY genes.
• Focus on gene context and NMD (nonsense-mediated decay) status.
• Comparison of heterozygous NMD-escape variants with other MODY causes.
• Identified heterozygous NMD-escape LOF variants in INS as a new cause of MODY.
• Demonstrated variability in pathogenicity based on gene context.
• Expanded the understanding of INS variants affecting MODY diagnosis.