Maturity-Onset Diabetes of the Young (MODY): Genetic Causes, Clinical Characteristics, Considerations for Testing, and Treatment Options
Abstract
:1. Introduction
2. MODY Subtypes and Associated Genetic Mutations
2.1. HNF1A MODY (MODY 3)
2.2. GCK MODY (MODY 2)
2.3. HNF4A MODY (MODY 1)
2.4. HNF1B MODY (MODY 5)
2.5. PDX1/IPF1-MODY (MODY 4)
2.6. NEUROD1 MODY (MODY 6)
2.7. KLF11 MODY (MODY 7)
2.8. CEL MODY (MODY 8)
2.9. PAX4 MODY (MODY 9)
2.10. INS MODY (MODY 10)
2.11. BLK MODY (MODY 11)
2.12. ABCC8 MODY (MODY 12)
2.13. KCNJ11 MODY (MODY 13)
2.14. APPL1 MODY (MODY 14)
3. Clinical Presentation
3.1. HNF1a (MODY 3)
3.2. GCK (MODY 2)
3.3. HNF4a (MODY 1)
3.4. HNF1b (MODY 5)
3.5. PDX1 (MODY 4)
3.6. NEUROD1 (MODY 6)
3.7. KLF11 (MODY 7)
3.8. CEL (MODY 8)
3.9. PAX4 (MODY 9)
3.10. INS (MODY 10)
3.11. BLK (MODY 11)
3.12. ABCC8 (MODY 12) and KCNJ11 (MODY 13)
3.13. APPL1 (MODY 14)
4. Indications for Testing
4.1. General Considerations
4.2. Patients with Fasting Hyperglycemia or IGT
4.3. Patients with Positive Diabetes Autoantibodies
5. Treatment
6. Conclusions
Funding
Institutional Review Board Statement
Informed Consent Statement
Conflicts of Interest
References
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Gene | Subtype | Chromosome | Effect on Beta Cell Function |
---|---|---|---|
HNF1a | MODY 3 | 12q24.2 | Insufficient glucose mediated insulin secretion |
GCK | MODY 2 | 7p15–p13 | Higher glucose threshold for insulin release, preserved beta cell secretion capacity |
HNF4 | MODY 1 | 20q13.2 | Insufficient glucose-mediated insulin secretion; progressive beta cell dysfunction |
HNF1b | MODY 5 | 17q12 | Beta cell dysfunction, possible pancreatic agenesis/atrophy |
PDX | MODY 4 | 13q12.2 | Impaired beta cell differentiation, impaired glucose-mediated insulin secretion |
NEUROD1 | MODY 6 | 2q32 | Beta cell dysfunction; insulinopenia or insulin resistance |
KLF11 | MODY 7 | 2q25 | Impaired insulin biosynthesis, impaired glucose-mediated insulin secretion |
CEL | MODY 8 | 9q34 | Beta cell dysfunction from protein misfolding and aggregation; pancreatic atrophy |
PAX4 | MODY 9 | 7q32 | Impaired beta cell maturation; impaired glucose-mediated insulin secretion |
INS | MODY 10 | 11p15.5 | Beta cell apoptosis, progressive decrease in beta cell mass |
BLK | MODY 11 | 8p23 | Decreased beta cell mass; impaired glucose-mediated insulin secretion |
ABCC8 | MODY 12 | 11.15 | Impaired insulin secretion |
KCJN11 | MODY 13 | 11p15 | Impaired insulin secretion |
APPL1 | MODY 14 | 3p14.3 | Reduced beta cell survival; impaired glucose-mediated insulin secretion |
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Antal, Z. Maturity-Onset Diabetes of the Young (MODY): Genetic Causes, Clinical Characteristics, Considerations for Testing, and Treatment Options. Endocrines 2021, 2, 485-501. https://doi.org/10.3390/endocrines2040043
Antal Z. Maturity-Onset Diabetes of the Young (MODY): Genetic Causes, Clinical Characteristics, Considerations for Testing, and Treatment Options. Endocrines. 2021; 2(4):485-501. https://doi.org/10.3390/endocrines2040043
Chicago/Turabian StyleAntal, Zoltan. 2021. "Maturity-Onset Diabetes of the Young (MODY): Genetic Causes, Clinical Characteristics, Considerations for Testing, and Treatment Options" Endocrines 2, no. 4: 485-501. https://doi.org/10.3390/endocrines2040043
APA StyleAntal, Z. (2021). Maturity-Onset Diabetes of the Young (MODY): Genetic Causes, Clinical Characteristics, Considerations for Testing, and Treatment Options. Endocrines, 2(4), 485-501. https://doi.org/10.3390/endocrines2040043