1Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea
2Department of Internal Medicine, Uijeongbu St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Uijeongbu, Korea
3Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
4Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University College of Medicine, Seoul, Korea
Copyright © 2020 Korean Diabetes Association
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CONFLICTS OF INTEREST
No potential conflict of interest relevant to this article was reported.
Gene | Methods | Subjects | Finding | Year | Reference |
---|---|---|---|---|---|
HNF1A | SSCP technique | 69 Early onset T2DM | 1/69 (1.5%) Synonymous mutation | 2001 | [18] |
HNF1A | Sanger sequencing | 16 Early onset T2DM | 1/16 (6.25%) Nonsynonymous mutation (R263L) | 2003 | [19] |
HNF1A | DNA chip | 22 Early onset T2DM | 1/22 (4.5%) Promoter polymorphism, non-segregating | 2004 | [20] |
HNF4A, GCK, HNF1A | Sanger sequencing | 23 MODY, 17 early onset T2DM | 2/40 (5%) HNF1A (P393fsdelC, promoter) | 2006 | [21] |
1/40 (2.5%) GCK (R191W) | |||||
1/40 (2.5%) HNF4A (T130I, polymorphism) | |||||
HNF1A | DNA chip | 25 Early onset T2DM | 1/25 (4%) Promoter polymorphism | 2008 | [22] |
HNF1A | Sanger sequencing | 96 GDM | 5/96 (5.2%) 2 Promoter, Arg278Gln, Pro300pro, IVS5 +106A>G | 2008 | [23] |
HNF1B | Sanger sequencing | 1 MODY | P159L mutation | 2014 | [24] |
PTPRD, SYT9, WFS1 | WES | 6 MODY | 3 Variants (Thr207Ile in PTPRD, Gln187Glu in SYT9, Val509Gly in WFS1) | 2015 | [25] |
HNF4A, ABCC8, HNF1A | WES | 28 Early onset T2DM | 4 Pathogenic/likely pathogenic variants (Leu319Pro in HNF4A, His103Tyr and Arg74Gln in ABCC8, Leu139Val in HNF1A) | 2016 | [26] |
6 Non-silent variants | |||||
GCK | WES | 3 Suspected MODY | 2 Variants (Leu30Pro, Ser83Leu) | 2017 | [27] |
GCK, HNF1A, HNF4A, HNF1B | Targeted panel sequencing | 109 Suspected monogenic diabetes | 14/109 (12.8%): MODY (7 GCK, 3 HNF1A, 3 HNF4A, 1 HNF1B) | 2019 | [14] |
5/109 (4.6%): mitochondrial MT-TL1 | |||||
4/109 (3.7%): WFS1, INS, ABCC8, FOXP3 |
Gene | Pathophysiology | Clinical feature | Frequency of microvascular complication | Treatment |
---|---|---|---|---|
HNF4A | β-cell dysfunction | Macrosomia | Frequent | Sensitive to SU |
Transient neonatal hyperinsulinemic hypoglycemia | ||||
Progressive insulin secretory defect | ||||
GCK | β-cell dysfunction (glucose sensing defect) | Stable mild fasting hyperglycemia at birth | Rare | Diet and exercise |
Typically asymptomatic | ||||
HNF1A | β-cell dysfunction; mainly insulin secretory defect | Transient neonatal hyperinsulinemic hypoglycemia | Frequent | Sensitive to SU |
Progressive insulin secretory defect | ||||
Renal glycosuria | ||||
PDX1 | β-cell dysfunction | Pancreatic agenesis | Unknown | Diet/OAD/insulin |
Overweight/obesity in some | ||||
HNF1B | β-cell dysfunction | IUGR | Frequent | Insulin |
Renal anomalies | ||||
Urogenital tract anomalies | ||||
Pancreatic hypoplasia | ||||
NEUROD1 | β-cell dysfunction | Homozygote: permanent neonatal diabetes and neurological abnormalities | Unknown | OAD/insulin |
Overweight/obesity in some | ||||
KLF11 | Decreased glucose sensitivity of β-cell | Similar to type 2 diabetes mellitus | Unknown | OAD/insulin |
CEL | Pancreatic endocrine and exocrine dysfunction | Pancreatic atrophy → exocrine pancreatic insufficiency | Unknown | OAD/insulin |
Fibrosis & lipomatosis → diabetes | ||||
PAX4 | β-cell dysfunction | Possible ketoacidosis | Unknown | Diet/OAD/insulin |
INS | β-cell dysfunction | Permanent neonatal diabetes | Unknown | Diet/OAD/insulin |
BLK | Insulin secretion defect | Overweight/obesity in some | Unknown | Diet/OAD/insulin |
ABCC8 | ATP-sensitive potassium channel dysfunction | Similar to HNF1A- and HNF4A-MODY | Unknown | Sensitive to SU |
KCNJ11 | ATP-sensitive potassium channel dysfunction | Transient and permanent neonatal diabetes | Unknown | OAD/insulin |
Overweight/obesity in some | ||||
APLL1 | Insulin secretion defect | Overweight/obesity in some | Unknown | Diet/OAD/insulin |
Gene | Methods | Subjects | Finding | Year | Reference |
---|---|---|---|---|---|
HNF1A | SSCP technique | 69 Early onset T2DM | 1/69 (1.5%) Synonymous mutation | 2001 | [18] |
HNF1A | Sanger sequencing | 16 Early onset T2DM | 1/16 (6.25%) Nonsynonymous mutation (R263L) | 2003 | [19] |
HNF1A | DNA chip | 22 Early onset T2DM | 1/22 (4.5%) Promoter polymorphism, non-segregating | 2004 | [20] |
HNF4A, GCK, HNF1A | Sanger sequencing | 23 MODY, 17 early onset T2DM | 2/40 (5%) HNF1A (P393fsdelC, promoter) | 2006 | [21] |
1/40 (2.5%) GCK (R191W) | |||||
1/40 (2.5%) HNF4A (T130I, polymorphism) | |||||
HNF1A | DNA chip | 25 Early onset T2DM | 1/25 (4%) Promoter polymorphism | 2008 | [22] |
HNF1A | Sanger sequencing | 96 GDM | 5/96 (5.2%) 2 Promoter, Arg278Gln, Pro300pro, IVS5 +106A>G | 2008 | [23] |
HNF1B | Sanger sequencing | 1 MODY | P159L mutation | 2014 | [24] |
PTPRD, SYT9, WFS1 | WES | 6 MODY | 3 Variants (Thr207Ile in PTPRD, Gln187Glu in SYT9, Val509Gly in WFS1) | 2015 | [25] |
HNF4A, ABCC8, HNF1A | WES | 28 Early onset T2DM | 4 Pathogenic/likely pathogenic variants (Leu319Pro in HNF4A, His103Tyr and Arg74Gln in ABCC8, Leu139Val in HNF1A) | 2016 | [26] |
6 Non-silent variants | |||||
GCK | WES | 3 Suspected MODY | 2 Variants (Leu30Pro, Ser83Leu) | 2017 | [27] |
GCK, HNF1A, HNF4A, HNF1B | Targeted panel sequencing | 109 Suspected monogenic diabetes | 14/109 (12.8%): MODY (7 GCK, 3 HNF1A, 3 HNF4A, 1 HNF1B) | 2019 | [14] |
5/109 (4.6%): mitochondrial MT-TL1 | |||||
4/109 (3.7%): WFS1, INS, ABCC8, FOXP3 |
MODY, maturity-onset diabetes of young; SU, sulfonylurea; OAD, oral antidiabetic agents; IUGR, intrauterine growth restriction.
SSCP, single-strand conformation polymorphsm; T2DM, type 2 diabetes mellitus; MODY, maturity-onset diabetes of young; GDM, gestational diabetes mellitus; WES, whole exome sequencing.