Fig. 1Diagnostic algorithm for maturity-onset diabetes of the young (MODY). T1DM, type 1 diabetes mellitus; T2DM, type 2 diabetes mellitus.
Table 1Clinical and molecular characteristics of MODY subtypes
MODY gene |
Chromosomal location |
Frequency (% from MODYs) |
Pathophysiology |
Other features |
Treatment |
HNF4A |
20q13 |
5 |
β-Cell dysfunction |
Neonatal hyperinsulinemia, low triglycerides |
Sensitive to sulfonylurea |
GCK |
7p13 |
15-20 |
β-Cell dysfunction (glucose sensing defect) |
Fasting hyperglycemia from newborn |
Diet |
HNF1A |
12q24 |
30-50 |
β-Cell dysfunction |
Glycosuria |
Sensitive to sulfonylurea |
PDX1/IPF1 |
13q12 |
<1 |
β-Cell dysfunction |
Homozygote: pancreatic agenesis |
Diet or OAD or insulin |
HNF1B |
17q12 |
5 |
β-Cell dysfunction |
Renal anomalies, genital anomalies, pancreatic hypoplasia |
insulin |
NEUROD1 |
2q31 |
<1 |
β-Cell dysfunction |
Adult onset diabetes |
OAD or insulin |
KLF11 |
2p25 |
<1 |
β-Cell dysfunction |
Similar to type 2 diabetes mellitus |
OAD or insulin |
CEL |
9q34 |
<1 |
Pancreas endocrine and exocrine dysfunction |
Exocrine insufficiency, lipomatosis |
OAD or insulin |
PAX4 |
7q32 |
<1 |
β-Cell dysfunction |
Possible ketoacidosis |
Diet or OAD or insulin |
INS |
11p15 |
<1 |
Insulin gene mutation |
Can also present PNDM |
OAD or insulin |
BLK |
8p23 |
<1 |
Insulin secretion defect |
Overweight, relative insulin secretion defect |
Diet or OAD or insulin |
ABCC8 |
11p15 |
<1 |
ATP-sensitive potassium channel dysfunction |
Homozygote: permanent neonatal diabetes; heterozygote: transient neonatal diabetes |
OAD (sulfonylurea) |
KCNJ11 |
11p15 |
<1 |
ATP-sensitive potassium channel dysfunction |
Homozygote: neonatal diabetes |
Diet or OAD or insulin |
Table 2MODY studies in Korean subjects
Gene |
Subjects |
Finding |
Reference |
HNF1A |
69 early onset T2DM |
One silent mutation |
[58] |
HNF1A |
16 early onset T2DM |
One missense (R236L) mutation |
[20] |
HNF1A |
22 early onset T2DM |
One mutation (promoter) |
[59] |
HNF4A, GCK, HNF1A |
23 MODY and 17 early onset T2DM |
One HNF1A (P393fsdelC, promoter) |
[5] |
One GCK (R191W) |
One HNF4A (T130I polymorphism) |
HNF1A |
25 early-onset T2DM |
Four promoter polymorphism |
[60] |
HNF1A |
96 GDM |
Five mutations ( 2 promoter, Arg278Gln, Pro300pro, IVS5 + 106A>G) |
[62] |
HNF1B |
1 MODY |
One missense (P159L) mutation |
[38] |
PTPRD, SYT9, WFS1 |
6 MODY |
Thr207Ile in PTPRD, Gln187Glu in SYT9, Val509Gly in WFS1 by whole-exome sequencing |
[57] |