Monogenic Forms of Diabetes Mellitus

Area of Science:

• Endocrinology
• Genetics
• Molecular Biology

Background:

• Diabetes mellitus encompasses common types and rarer monogenic forms.
• Maturity-onset diabetes of the young (MODY) and neonatal diabetes mellitus (NDM) are significant monogenic subtypes.
• MODY is often underdiagnosed or misdiagnosed, while NDM is a severe condition presenting in infancy.

Purpose of the Study:

• To highlight the importance of genetic testing in diagnosing monogenic diabetes forms.
• To differentiate between MODY and NDM based on genetic causes and clinical presentation.
• To emphasize recent advancements in genetic testing technologies for these conditions.

Main Methods:

• Review of identified MODY genes (e.g., HNF1A, GCK, HNF4A).
• Description of genetic causes for neonatal diabetes mellitus (e.g., KCNJ11, ABCC8 mutations).
• Advancement in genetic testing from sequential to simultaneous next-generation sequencing for MODY.

Main Results:

• Over a dozen MODY genes identified, with HNF1A, GCK, and HNF4A being most prevalent.
• NDM incidence is 1:100,000-1:400,000 live births, with permanent NDM accounting for half.
• Mutations in KCNJ11 and ABCC8 are common causes of NDM.

Conclusions:

• Genetic classification is vital for MODY treatment and prognosis.
• NDM has seen successful clinical integration following molecular discoveries.
• Current guidelines recommend genetic testing for both MODY and NDM.