Klinische FragestellungDiabetes mellitus, genetisch bedingt; Differentialdiagnose

NGS +

[Sanger]

Während eine Minderheit der Diabetes-Patienten entweder von autoimmunen (Typ-1-Diabetes oder latentem Autoimmun-Diabetes bei Erwachsenen), monogenen oder sekundären (endokrinen) Formen betroffen ist, leiden >80% an Typ-2-Diabetes (T2D). T2D stellt wahrscheinlich ein Spektrum dar, das von rein monogenen Erkrankungen bis hin zu Formen reicht, bei denen schädliche Auswirkungen von Umweltfaktoren gegenüber einer genetischen Anfälligkeit überwiegen. Während der permanente Neugeborenen-Diabetes am einen Ende des Spektrums liegt, kann T2D bei älteren Menschen das entgegengesetzte Extrem darstellen. In 20% der Fälle von ND bleibt die genetische Ursache unbekannt. Monogener Nicht-Auto-Immun-Diabetes umfasst auch ein großes Spektrum an Phänotypen, nämlich Neugeborenen-Diabetes, Diabetes-assoziierte syndromale Erkrankungen, mitochondrialen Diabetes und vererbte familiäre Formen von früh einsetzendem Diabetes, "Maturity-Onset Diabetes of the Young" - MODY. Obwohl Mutationen in mindestens 14 verschiedenen Genen mit MODY in Verbindung gebracht werden, bleibt das verursachende Gen bei 10 % dieser Patienten unbekannt. Der Anteil des monogenen Diabetes bei Patienten, die vor dem Alter von 45 Jahren diagnostiziert werden, liegt wahrscheinlich bei 3-5 %. Negative molekulargenetische Ergebnisse schließen die klinische Diagnose keinesfalls aus.

(Basisdiagnostik-Gene: ###; zusätzliche Gene: ###)

Referenzen: https://www.ncbi.nlm.nih.gov/books/NBK1447/

https://www.ncbi.nlm.nih.gov/books/NBK500456/https://www.ncbi.nlm.nih.gov/books/NBK476444/https://www.ncbi.nlm.nih.gov/books/NBK4144/

• Alias: Familial diabetes
• Alias: Rare genetic diabetes mellitus
• Allelic: Agammaglobulinemia 7, AR (PIK3R1)
• Allelic: Aniridia (PAX6)
• Allelic: Anterior segment dysgenesis 5, multiple subtypes (PAX6)
• Allelic: Atrial septal defect 2 (GATA4)
• Allelic: Atrial septal defect 9 (GATA6)
• Allelic: Atrioventricular septal defect 4 (GATA4)
• Allelic: Atrioventricular septal defect 5 (GATA)6
• Allelic: Cardiomyopathy, dilated, 1A (LMNA)
• Allelic: Carotid intimal medial thickness 1 (PPARG)
• Allelic: Cataract 41 (WFS1)
• Allelic: Cataract with late-onset corneal dystrophy (PAX6)
• Allelic: Charcot-Marie-Tooth disease, type 2B1 (LMNA)
• Allelic: Coloboma of optic nerve (PAX6
• Allelic: Coloboma, ocular (PAX6)
• Allelic: Colorectal cancer, susceptibility to, 10 (POLD1)
• Allelic: Deafness, AD 6/14/38 (WFS1)
• Allelic: Emery-Dreifuss muscular dystrophy 2, AD (LMNA)
• Allelic: Emery-Dreifuss muscular dystrophy 3, AR (LMNA)
• Allelic: Fanconi-Bickel syndrome (SLC2A2)
• Allelic: Foveal hypoplasia 1 (PAX6)
• Allelic: Heart-hand syndrome, Slovenian type (LMNA)
• Allelic: Hepatic adenoma, somatic (HNF1A)
• Allelic: Hyper-IgE recurrent infection syndrome (STAT3)
• Allelic: Hyperinsulinemic hypoglycemia, familial, 2 (KCNJ11)
• Allelic: Hyperinsulinemic hypoglycemia, familial, 5 (INSR)
• Allelic: Hyperproinsulinemia (INS)
• Allelic: Hypoinsulinemic hypoglycemia with hemihypertrophy (AKT2)
• Allelic: Immunodeficiency 36 PIK3R1)
• Allelic: Keratitis (PAX6)
• Allelic: Leprechaunism (INSR)
• Allelic: Malouf syndrome (LMNA)
• Allelic: Mandibuloacral dysplasia (LMNA)
• Allelic: Morning glory disc anomaly (PAX6)
• Allelic: Muscular dystrophy, congenital (LMNA)
• Allelic: Neuropathy, distal hereditary motor, type VC (BSCL2)
• Allelic: Obesity, resistance to (PPARG)
• Allelic: Obesity, severe (PPARG)
• Allelic: Optic nerve hypoplasia (PAX6)
• Allelic: Persistent truncus arteriosus (GATA6)
• Allelic: Renal cell carcinoma (HNF1A. HNF1B)
• Allelic: Restrictive dermopathy, lethal (LMNA)
• Allelic: Restrictive dermopathy, lethal (ZMPSTE24)
• Allelic: Silver spastic paraplegia syndrome (BSCL2)
• Allelic: Testicular anomalies with/-out congenital heart disease (GATA4)
• Allelic: Tetralogy of Fallot (GATA4)
• Allelic: Tetralogy of Fallot (GATA6)
• Allelic: Ventricular septal defect 1 (GATA4)
• Allelic: Vissers-Bodmer syndrome (CNOT1)
• Abdominal obesity-metabolic syndrome 3 (DYRK1B)
• Asphyxiating thoracic dystrophy syndrome + infantile‐onset diabetes [panelapp] (PDIA6)
• Ataxia, combined cerebellar + peripheral, with hearing loss + diabetes mellitus (DNAJC3)
• Autoimmune disease, multisystem, infantile-onset, 1 (STAT3)
• Currarino syndrome (MNX1)
• Diabetes [panelapp] (PAX6)
• Diabetes mellitus, insulin-dependent (HNF1A)
• Diabetes mellitus, insulin-dependent, 2 (INS)
• Diabetes mellitus, insulin-dependent, 20 (HNF1A)
• Diabetes mellitus, insulin-resistant, with acanthosis nigricans (INSR)
• Diabetes mellitus, ketosis-prone, susceptibility to (NKX2-2)
• Diabetes mellitus, ketosis-prone, susceptibility to (PAX4)
• Diabetes mellitus, neonatal, with congenital hypothyroidism (GLIS3)
• Diabetes mellitus, noninsulin-dependent (ABCC8)
• Diabetes mellitus, noninsulin-dependent (HNF4A)
• Diabetes mellitus, noninsulin-dependent (SLC2A2)
• Diabetes mellitus, noninsulin-dependent, 2 (HNF1A)
• Diabetes mellitus, noninsulin-dependent, association with (WFS1)
• Diabetes mellitus, noninsulin-dependent, late onset (GCK)
• Diabetes mellitus, permanent neonatal 1 (GCK)
• Diabetes mellitus, permanent neonatal 3, with/-out neurologic features (ABCC8)
• Diabetes mellitus, permanent neonatal 4 (INS)
• Diabetes mellitus, transient neonatal 1 (ZPF57)
• Diabetes mellitus, transient neonatal 2 (ABCC8)
• Diabetes mellitus, transient neonatal 3 (KCNJ11)
• Diabetes mellitus, type 2 (AKT2, NKX2-2, PAX4)
• Diabetes mellitus, type II, susceptibility to (KCNJ11, PDX1)
• Diabetes, mellitus, insulin-dependent, susceptibility to, 10 (IL2RA)
• Diabetes, permanent neonatal 2, with/-out neurologic features (KCNJ11)
• Diabetes, type 2 (PPARG)
• Diarrhea 4, malabsorptive, congenital (NEUROG3)
• Encephalopathy, progressive, with or without lipodystrophy (BSCL2)
• Fanconi renotubular syndrome 4, with maturity-onset diabetes of the young (HNF4A)
• Histiocytosis-lymphadenopathy plus syndrome (SLC29A3)
• Holoprosencephaly 12, with or without pancreatic agenesis (CNOT1)
• Hutchinson-Gilford progeria (LMNA)
• Hyperinsulinemic hypoglycemia, familial, 1 (ABCC8)
• Hyperinsulinemic hypoglycemia, familial, 3 (GCK)
• Hyperphenylalaninemia, BH4-deficient, D (PCBD1)
• Hypoglycemia of infancy, leucine-sensitive (ABCC8)
• Immunodeficiency 41 with lymphoproliferation + autoimmunity (IL2RA)
• Immunodeficiency, common variable, 8, with autoimmunity (LRBA)
• Immunodysregulation, polyendocrinopathy + enteropathy, XL (FOXP3)
• Insulin resistance, severe, digenic (PPARG)
• Leukoencephalopathy with vanishing white matter 1, +/- ovarian failure (EIF2B1)
• Lipodystrophy, congenital generalized, type 1 (AGPAT2)
• Lipodystrophy, congenital generalized, type 2 (BSCL2)
• Lipodystrophy, familial partial, type 2 (LMNA)
• Lipodystrophy, familial partial, type 3 (PPARG)
• Lipodystrophy, familial partial, type 4 (PLIN1)
• MEHMO [Mental retard., Epilepsy, Hypogonadism/-genitalism, Microcephaly, Obesity] syndrome (EIF2S3)
• MODY, type I (HNF4A)
• MODY, type II (GCK)
• MODY, type III (HNF1A)
• MODY, type IV (PDX1)
• MODY, type IX (NKX2-2)
• 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)
• Mandibular hypoplasia, deafness, progeroid features + lipodystrophy syndrome (POLD1)
• Mandibuloacral dysplasia with type B lipodystrophy (ZMPSTE24)
• Microcephaly, epilepsy + diabetes syndrome (IER3IP1)
• Microcephaly, epilepsy + diabetes syndrome 2 (YIPF5)
• Microcephaly, short stature + impaired glucose metabolism 1 (TRMT10A)
• Microcephaly, short stature + impaired glucose metabolism 2 (PPP1R15B)
• Mitchell-Riley syndrome (RFX6)
• Neonatal diabetes mellitus [MONDO:0016391, panelapp] (ONECUT1)
• Neonatal diabetes mellitus [MONDO:0016391, panelapp] (ZNF808)
• Neonatal diabetes mellitus [MONDO:0016391] (IL2RA)
• ONECUT1-associated neonatal diabetes [panelapp] (ONECUT1)
• Pancreatic + cerebellar agenesis (PTF1A)
• Pancreatic agenesis + congenital heart defects (GATA6)
• Pancreatic agenesis 1 (PDX1)
• Pancreatic agenesis 2 (PTF1A)
• Pancreatic agenesis [MONDO:0009832, panelapp] (ZNF808)
• Primrose syndrome (ZBTB20)
• Rabson-Mendenhall syndrome (INSR)
• Renal cysts + diabetes syndrome (HNF1B)
• SHORT syndrome (PIK3R1)
• Short stature, microcephaly + endocrine dysfunction (XRCC4)
• Thiamine-responsive megaloblastic anemia syndrome (SLC19A2)
• Type 2 diabetes mellitus (HNF1B)
• Type 2 diabetes mellitus, susceptibility to (NEUROD1)
• Wolcott-Rallison syndrome (EIFAK3)
• Wolfram syndrome 1 (WFS1)
• Wolfram syndrome 2 (CISD2)
• Wolfram-like syndrome, AD (WFS1)
• Woodhouse-Sakati syndrome (DCAF17)