This analysis highlights the interplay between GCK-MODY mutation and insulin resistance, suggesting significant genetic contributions to diabetic phenotypes.
Key Points
The novel GCK-Q26L mutation demonstrates pathogenic attributes associated with GCK-MODY.
The proband exhibited severe diabetic symptoms despite inheriting the mutation from a parent with mild hyperglycemia.
Whole-exome sequencing and polygenic risk score analysis revealed high insulin resistance linked to severe phenotypes.
Dorzagliatin and liraglutide improved glucose tolerance in a mouse model, indicating potential therapeutic avenues.