IllnessDiabetes mellitus, MODY

NGS +

[Sanger]

MODY is the most common form of monogenic diabetes. The clinical features of MODY vary according to genetic aetiology. Most common subtypes are HNF1A-MODY (30-50%), GCK-MODY (30-50%), HNF4A-MODY (10%) and HNF1B-MODY (1-5%). The latter is also known as kidney cysts and diabetes syndrome. At least nine other less common genetic subtypes have been described. Patients with HNF1A and HNF4A mutations have slowly progressive beta cell dysfunction. Vascular complications of diabetes are observed with a similar frequency to type 1 or type 2 diabetes. GCK-associated MODY is characterised by asymptomatic, non-progressive mild fasting hyperglycaemia with low postprandial glucose excursions from birth and is not associated with vascular complications. Indications for genetic testing for MODY include the occurrence of diabetes in adolescence or young adulthood, maintenance of endogenous insulin production and usually a significant family history of diabetes. Inheritance is usually autosomal dominant; penetrance values vary according to mutated genes.

Reference: https://www.ncbi.nlm.nih.gov/books/NBK500456/

• CAVE BLK, KLF11, PAX4 genes: evidence for causing MODY needs to be expanded/confirmed
• Allelic: Cataract 41 (WFS1)
• Allelic: Deafness, AD 6/14/38 (WFS1)
• Allelic: Diabetes mellitus, insulin-dependent (HNF1A)
• Allelic: Diabetes mellitus, insulin-dependent, 20 (HNF1A)
• Allelic: Diabetes mellitus, ketosis-prone, susceptibility to (PAX4)
• Allelic: Diabetes mellitus, noninsulin-dependent (ABCC8, HNF1B, HNF4A)
• Allelic: Diabetes mellitus, noninsulin-dependent, 2 (HNF1A)
• Allelic: Diabetes mellitus, noninsulin-dependent, late onset (GCK)
• Allelic: Diabetes mellitus, permanent neonatal (ABCC8, GCK, INS)
• Allelic: Diabetes mellitus, permanent neonatal, with neurologic features (KCNJ11)
• Allelic: Diabetes mellitus, transient neonatal 2 (ABCC8)
• Allelic: Diabetes mellitus, transient neonatal, 3 (KCNJ11)
• Allelic: Diabetes mellitus, type 1 (INS)
• Allelic: Diabetes mellitus, type 2 (PAX4)
• Allelic: Diabetes mellitus, type 2, susceptibility to (KCNJ11, PDX1, NEUROD1)
• Allelic: Hepatic adenoma, somatic (HNF1A)
• Allelic: Hyperinsulinemic hypoglycemia, familial, 1 (ABCC8)
• Allelic: Hyperinsulinemic hypoglycemia, familial, 2 (KCNJ11)
• Allelic: Hyperinsulinemic hypoglycemia, familial, 3 (GCK)
• Allelic: Hyperproinsulinemia (INS)
• Allelic: Hypoglycemia of infancy, leucine-sensitive (ABCC8)
• Allelic: Pancreatic agenesis 1 (PDX1)
• Allelic: Renal cell carcinoma (HNF1A, HNF1B)
• Allelic: Renal cysts and diabetes syndrome (HNF1B)
• Diabetes mellitus, noninsulin-dependent, association with (WFS1)
• Fanconi renotubular syndrome 4, with MODY (HNF4A)
• MODY, type I (HNF4A)
• MODY, type II (GCK)
• MODY, type III (HNF1A)
• MODY, type IV (PDX1)
• MODY, type IX (PAX4)
• MODY, type VI (NEUROD1)
• MODY, type VII (KLF11)
• MODY, type VIII (CEL)
• MODY, type X (INS)
• MODY, type XI (BLK)
• MODY, type XIII (KCNJ11)
• MODY, type XIV (APPL1)
• Mitchell-Riley s.: neonat. diab., pancreatic hypopl., intest. atresia, gallbladder a-/hypopl. (RFX6)
• Wolfram syndrome 1 (WFS1)
• Wolfram-like syndrome, AD (WFS1)