Monogenic diabetes: An evidence-based clinical approach

Area of Science:

• Genetics
• Endocrinology
• Molecular Biology

Background:

• Monogenic diabetes results from single-gene defects, leading to hyperglycemia.
• Maturity-onset diabetes of the young (MODY) encompasses 14 subtypes, often misdiagnosed as type 1 or type 2 diabetes.
• Neonatal diabetes mellitus (NDM) is a rare form presenting within the first six months of life.

Purpose of the Study:

• To highlight the heterogeneity of monogenic diabetes and its subtypes.
• To emphasize the diagnostic challenges and the role of genetic testing.
• To discuss the impact of advanced sequencing technologies on diagnosis and treatment.

Main Methods:

• Review of monogenic diabetes subtypes, including MODY and NDM.
• Discussion of diagnostic tools like biomarkers, scoring systems, and genetic testing.
• Exploration of next-generation sequencing (NGS) technologies (panels, WES, WGS).

Main Results:

• Genetic testing identifies specific mutations in genes like GCK, HNF4A, HNF1A, HNF1B, KCNJ11, and ABCC8.
• NGS technologies have expanded diagnostic capabilities beyond older methods.
• Challenges include interpreting variants of unknown significance (VUS).

Conclusions:

• Monogenic diabetes diagnosis is crucial for precision treatment, particularly for NDM and certain MODY subtypes.
• Advances in genetic testing offer improved diagnostic accuracy and personalized therapeutic strategies.
• Ethical considerations and variant interpretation remain important aspects of genetic testing in monogenic diabetes.