Figure1
Mutations in syndromic neonatal diabetes mellitus_
| Mechanism | Gene Mutation | Chromosome Locus | Inheritance | Additional Features |
|---|---|---|---|---|
| Fanconi-Bickel syndrome | SCL2A2 (GLUT2) | 3q26.1-26.3 | AR | hypergalatosemia; liver dysfunction |
| Roger syndrome | SCL19A2 | 1q23.3 | AR | thiamine-sensorinueral responsive deafness megaloblastic anemia; |
| Abnormal development pancreatic | RFX6 | 6q22.1 | AR | intestinal atresia + bladder agenesis |
| GATA6 | 18q11-q11.2 | AD | pancreatic biliary abnormalities agenesis; heart defects; | |
| GATA4 | 8p23.1 | AD | pancreatic agenesis + heart defects | |
| GLIS3 | 9p24.3-p23 | AR | congenital hepatic fibrosis; hypothyridism; renal cysts glaucoma; | |
| NEURG3 | 10q21.3 | AR | malabsorbtive diarrhea | |
| NEUROD1 | 2q32 | AR | cerebellar deafness hypoplasia; visual impairment; | |
| PAX6 | 11.p13 | AR | microphtalmia; brain malformations | |
| MNX1 | 7q36.3 | AR | developmental imperforate anus delay; sacral agenesis; | |
| MNX2-2 | 20p11.22 | AR | developmental deafness delay; hypotonia; short stature; | |
| PTF1 | 10.p12.2 | AR | pancreatic hypoplasia; cerebellar hypoplasia | |
| Destruction of β-cells | ||||
| Wolcott-Rallison syndrome | EIF2AK3 | 2p11.2 | de novo or AD | skeletal dysplasia; liver dysfunction |
| IER3IP1 | 18q21.2 | AR | microcephaly; lisencephaly; enceph-alopathy | |
| IPEX syndrome | FOXP3 | Xp11.23-p13.3 | X-recessive linked; | autoimmune autoimmune enteropathy; hypothyroidism; eczema |
| Wolfram (DIDMOAD)syndrome a | WFS1 | 4p16.1 | AR | optic atrophy; DM; DI |
| WFS1 | 4p16.1 | AD | congenital cataracts; deafness |
Gene mutations in transient neonatal diabetes mellitus_
| Mechanism of β-Cell Dysfunction | Gene Mutation | Chromosome Locus | Inheritance | Additional Features | Therapy |
|---|---|---|---|---|---|
| Reduced β-cell development | ZAC (IPLAG1)/ HYMA1 | 6q24 | imprinting; AD | macroglossia; umbilical hernia | insulin |
| ZEP57 | 6p22.1 | AR | insulin | ||
| HNF1B | 17q21.3 | AD | pancreatic cysts hypoplasia; renal | ||
| Failure membrane to depolarize | KCNJ11a (Kir6.2) | 11p15.1 | AD; de novo | low developmental birth weight; delay; DEND | sulfonylurea |
| Failure channel to close KATP | ABCC8a (SUR1) | 11p15.1 | AD; AR; de novo | low birth weight | sulfonylurea |
| Abnormal β-cell function | INSa (proinsulin) | 11p15.5 | AR | low birth weight | insulin |
Gene mutations in permanent neonatal diabetes mellitus_
| Mechanism of β-Cell Dysfunction | Gene Mutation | Chromosome Locus | Inheritance | Additional Features | Therapy |
|---|---|---|---|---|---|
| Failure membrane to depolarize | KCNJ11 (Kir6.2) | 11p15.1 | AD; de novo | low developmental birth weight; delay; DEND | sulfonylurea |
| Failure KATP channel to close | ABCC8 (SUR1) | 11p15.1 | de novo; AD; AR | low birth weight | sulfonylurea |
| Abnormal function β-cell | INS (proinsulin) | 11p15.5 | de novo; AD; AR | low birthweight | insulin |
| Abnormal sensing glucose | GCK | 7p15-13 | AR | ||
| Abnormal development pancreatic | PDX1 | 13.q12.1 | AR | pancreatic afenesis steatorrhea |