Monogenic diabetes is a rare form of diabetes caused by a mutation in a single gene, in contrast to type 1 and type 2 diabetes, which are polygenic and multifactorial. The two main forms are MODY (Maturity-Onset Diabetes of the Young), which develops before the age of 25, and Neonatal Diabetes Mellitus (NDM), which presents within the first 6 months of life.
Genetic testing plays a critical role, as monogenic diabetes is often misdiagnosed as type 1 or type 2 diabetes, leading to inappropriate treatments. Proper diagnosis allows for tailored therapeutic decisions, accurate prognosis, and family risk assessment.
GENOSOPHY® Monogenic Diabetes Panel – What It Covers
This test involves NGS sequencing of 68 genes and dozens of variants associated with:
- MODY (Maturity-Onset Diabetes of the Young)
Caused by mutations in HNF1A, HNF4A, GCK, HNF1B, and others.
- Typically appears before age 25
- Follows an autosomal dominant inheritance pattern
- Often managed effectively with oral antidiabetic medications (e.g., sulfonylureas) rather than insulin
- Neonatal Diabetes Mellitus (NDM)
- Occurs within the first 6 months of life
- Caused by mutations in genes like KCNJ11, ABCC8, INS
- Some forms respond to oral therapy instead of lifelong insulin
- Syndromic Forms of Monogenic Diabetes
- HNF1B-related diabetes (Renal Cysts and Diabetes Syndrome)
- Mitochondrial diabetes, including MIDD and MELAS syndrome
Who Should Consider This Test?
- Individuals diagnosed with diabetes before age 25 and negative for autoimmune markers
- People with a family history of diabetes affecting multiple generations
- Infants diagnosed with diabetes before 6 months of age
- Patients with atypical diabetes unresponsive to standard type 1 or 2 treatment
- Families with known pathogenic variants related to monogenic diabetes
Clinical Benefits
Diagnosis
- Identification of pathogenic mutations causing monogenic diabetes
- Accurate differentiation between type 1, type 2, and monogenic forms
Prognosis
- Assessment of complication risk
- Evaluation of familial diabetes risk
Management
- Treatment selection – insulin may be replaced with oral therapy (e.g., sulfonylureas)
- Tailored medical management and monitoring strategies
- Genetic counseling and preventive care for family members
Test Procedure
- Sample collection via saliva or blood
- Next-Generation Sequencing (NGS) of 68 genes and non-coding regulatory regions
- Results available within approximately 5 weeks
Optional: Detailed genetic counseling by Professors of the Medical School of the National and Kapodistrian University of Athens (NKUA)
Genes Included in the GENOSOPHY® Monogenic Diabetes Panel
ABCC8, APPL1, BLK, CEL*, EIF2AK3, FOXP3, GATA6, GCK, GLIS3, GLUD1*, HADH, HNF1A, HNF1B, HNF4A, INS, INSR, KCNJ11, KLF11, MT-ATP6, MT-ATP8, MT-CO1, MT-CO2, MT-CO3, MT-CYB, MT-ND1, MT-ND2, MT-ND3, MT-ND4, MT-ND4L, MT-ND5, MT-ND6, MT-RNR1, MT-RNR2, MT-TA, MT-TC, MT-TD, MT-TE, MT-TF, MT-TG, MT-TH, MT-TI, MT-TK, MT-TL1, MT-TL2, MT-TM, MT-TN, MT-TP, MT-TQ, MT-TR, MT-TS1, MT-TS2, MT-TT, MT-TV, MT-TW, MT-TY, NEUROD1, NEUROG3, PAX4, PDX1, PPARG, PTF1A, RFX6, SLC16A1, SLC2A2, UCP2, WFS1, ZFP57, ZNF814
Note: In addition to full exon sequencing, promoters, introns, and known non-coding pathogenic variants are analyzed.
Detection sensitivity for SNVs, indels, and CNVs is >99%. Slightly reduced sensitivity may occur in genes marked with an asterisk (*).
