PNDM
MCID: DBT083
MIFTS: 61

Diabetes Mellitus, Permanent Neonatal (PNDM)

Categories: Endocrine diseases, Genetic diseases, Metabolic diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Diabetes Mellitus, Permanent Neonatal

MalaCards integrated aliases for Diabetes Mellitus, Permanent Neonatal:

Name: Diabetes Mellitus, Permanent Neonatal 57 74 13 72
Permanent Neonatal Diabetes Mellitus 12 24 53 25 59 37 29 6 15
Pndm 57 12 53 25 59 74
Permanent Diabetes Mellitus of Infancy 12 53 74
Pdmi 57 12 74
Dend Syndrome 59 6
Diabetes, Permanent Neonatal, with or Without Neurologic Features 57
Diabetes Mellitus, Permanent Neonatal, with Neurologic Features 6
Diabetes Mellitus Permanent Neonatal with Neurologic Features 74
Developmental Delay-Epilepsy-Neonatal Diabetes Syndrome 59
Developmental Delay, Epilepsy, and Neonatal Diabetes 72
Developmental Delay Epilepsy and Neonatal Diabetes 74
Diabetes Mellitus, Permanent, of Infancy; Pdmi 57
Diabetes Mellitus, Permanent, of Infancy 57
Neonatal Diabetes Mellitus, Permanent 75
Monogenic Diabetes of Infancy 59
Dend 74

Characteristics:

Orphanet epidemiological data:

59
dend syndrome
Inheritance: Autosomal dominant,Autosomal recessive,Not applicable; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;
permanent neonatal diabetes mellitus
Inheritance: Autosomal dominant,Autosomal recessive; Prevalence: 1-9/1000000 (Europe),1-9/1000000 (United Kingdom),1-9/1000000 (Poland),1-9/1000000 (Netherlands),1-9/1000000 (Slovakia),1-9/1000000 (United States); Age of onset: Antenatal,Infancy,Neonatal;

OMIM:

57
Inheritance:
autosomal recessive
autosomal dominant

Miscellaneous:
diagnosis within the first 3 months of life
some patients do not show neurologic abnormalities or dysmorphic features
some patients show a favorable response to sulfonylurea treatment


HPO:

32
diabetes mellitus, permanent neonatal:
Inheritance autosomal dominant inheritance autosomal recessive inheritance


GeneReviews:

24
Penetrance Reduced penetrance has been seen in pndm caused by pathogenic variants in kcnj11 and abcc8 [flanagan et al 2007].

Classifications:



External Ids:

Disease Ontology 12 DOID:0060639
OMIM 57 606176
KEGG 37 H00512
MeSH 44 D003920
ICD10 via Orphanet 34 P70.2
UMLS via Orphanet 73 C1833104 C1853564
UMLS 72 C1833104 C1853564

Summaries for Diabetes Mellitus, Permanent Neonatal

OMIM : 57 Neonatal diabetes mellitus (NDM), defined as insulin-requiring hyperglycemia within the first 3 months of life, is a rare entity, with an estimated incidence of 1 in 400,000 neonates (Shield, 2000). In about half of the neonates, diabetes is transient (see 601410) and resolves at a median age of 3 months, whereas the rest have a permanent insulin-dependent form of diabetes (PNDM). In a significant number of patients with transient neonatal diabetes mellitus, type II diabetes (see 125853) appears later in life (Arthur et al., 1997). PNDM is distinct from childhood-onset autoimmune diabetes mellitus type I (IDDM; 222100). Massa et al. (2005) noted that the diagnostic time limit for PNDM has changed over the years, ranging from onset within 30 days of birth to 3 months of age. However, as patients with the clinical phenotype caused by mutation in the KCNJ11 gene have been identified with onset up to 6 months of age, Massa et al. (2005) suggested that the term 'permanent diabetes mellitus of infancy' (PDMI) replace PNDM as a more accurate description, and include those who present up to 6 months of age. The authors suggested that the new acronym be linked to the gene product (e.g., GCK-PDMI, KCNJ11-PDMI) to avoid confusion with patients with early-onset, autoimmune type I diabetes. Colombo et al. (2008) proposed that, because individuals with INS gene mutations may present with diabetes well beyond 6 months of age and cannot be distinguished from patients with type 1 diabetes except for the absence of type 1 diabetes autoantibodies, the term PNDM should be replaced with 'monogenic diabetes of infancy (MDI),' a broad definition including any form of diabetes, permanent or transient, with onset during the first years of life and caused by a single gene defect. (606176)

MalaCards based summary : Diabetes Mellitus, Permanent Neonatal, also known as permanent neonatal diabetes mellitus, is related to epiphyseal dysplasia, multiple, with early-onset diabetes mellitus and pancreatic agenesis, and has symptoms including seizures and muscle weakness. An important gene associated with Diabetes Mellitus, Permanent Neonatal is KCNJ11 (Potassium Inwardly Rectifying Channel Subfamily J Member 11), and among its related pathways/superpathways are Type II diabetes mellitus and Maturity onset diabetes of the young. The drugs Glyburide and Glucagon have been mentioned in the context of this disorder. Affiliated tissues include pancreas, heart and brain, and related phenotypes are hyperglycemia and failure to thrive

Disease Ontology : 12 A neonatal diabetes mellitus that has material basis in homozygous mutation in the glucokinase gene (GCK), heterozygous mutation in the KCNJ11 and INS genes, or by heterozygous or homozygous mutation in the ABCC8 gene.

Genetics Home Reference : 25 Permanent neonatal diabetes mellitus is a type of diabetes that first appears within the first 6 months of life and persists throughout the lifespan. This form of diabetes is characterized by high blood sugar levels (hyperglycemia) resulting from a shortage of the hormone insulin. Insulin controls how much glucose (a type of sugar) is passed from the blood into cells for conversion to energy. Individuals with permanent neonatal diabetes mellitus experience slow growth before birth (intrauterine growth retardation). Affected infants have hyperglycemia and an excessive loss of fluids (dehydration) and are unable to gain weight and grow at the expected rate (failure to thrive). In some cases, people with permanent neonatal diabetes mellitus also have certain neurological problems, including developmental delay and recurrent seizures (epilepsy). This combination of developmental delay, epilepsy, and neonatal diabetes is called DEND syndrome. Intermediate DEND syndrome is a similar combination but with milder developmental delay and without epilepsy. A small number of individuals with permanent neonatal diabetes mellitus have an underdeveloped pancreas. Because the pancreas produces digestive enzymes as well as secreting insulin and other hormones, affected individuals experience digestive problems such as fatty stools and an inability to absorb fat-soluble vitamins.

NIH Rare Diseases : 53 Permanent neonatal diabetes mellitus (PNDB) is a type of diabetes that appears within the first 6 months of life and persists throughout life. Affected individuals have slow growth before birth followed by hyperglycemia, dehydration and failure to thrive in infancy. Some individuals also have neurological problems including developmental delay and epilepsy; when these problems are present with PNDB, it is called DEND syndrome. A few individuals with PNDB also have an underdeveloped pancreas and may have digestive problems. PNDB is caused by mutations in any one of several genes (some of which have not yet been identified) including the KCNJ11, ABCC8, and INS genes. It may be inherited in an autosomal recessive or autosomal dominant manner. Treatment includes rehydration, insulin therapy and/or long-term therapy with oral sulfonylureas (in some cases).

KEGG : 37
Neonatal diabetes mellitus (NDM), which is a monogenic form of diabetes, is a heterogeneous group of disorders characterized by hyperglycemia in the first 6 months of life. NDM is categorized into transient (TNDM) and permanent (PNDM). In the case of PNDM, the condition does not resolve over time. The most frequent causes of PNDM are heterozygous mutations in the KCNJ11, INS and ABCC8 genes that play a critical role in insulin secretion from pancreatic beta-cells. The responsible genes remain unknown in up to 40% of patients.

UniProtKB/Swiss-Prot : 74 Diabetes mellitus, permanent neonatal: A rare form of diabetes distinct from childhood-onset autoimmune diabetes mellitus type 1. It is characterized by insulin-requiring hyperglycemia that is diagnosed within the first months of life. Permanent neonatal diabetes requires lifelong therapy.

Wikipedia : 75 Permanent neonatal diabetes mellitus (PNDM) is a newly identified and potentially treatable form of... more...

GeneReviews: NBK1447

Related Diseases for Diabetes Mellitus, Permanent Neonatal

Diseases related to Diabetes Mellitus, Permanent Neonatal via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 78)
# Related Disease Score Top Affiliating Genes
1 epiphyseal dysplasia, multiple, with early-onset diabetes mellitus 32.7 KCNJ11 EIF2AK3 ABCC8
2 pancreatic agenesis 32.5 PTF1A PDX1 KCNJ11 INS GCK ABCC8
3 hypoglycemia 30.9 KCNJ11 INS GCK ABCC8
4 maturity-onset diabetes of the young, type 2 30.6 PDX1 INS GCK
5 gestational diabetes 30.6 KCNJ11 INS GCK
6 maturity-onset diabetes of the young, type 4 30.6 PDX1 GCK
7 diabetes mellitus, noninsulin-dependent 30.2 PDX1 KCNJ11 INS GCK ABCC8
8 hyperglycemia 30.1 PDX1 KCNJ11 INS GCK ABCC8
9 monogenic diabetes 30.0 SLC19A2 PDX1 KCNJ11 INS GCK ABCC8
10 neonatal diabetes mellitus 29.2 SLC19A2 PTF1A PDX1 KCNJ11 INS GLIS3
11 maturity-onset diabetes of the young 29.2 PDX1 NKX6-1 MNX1 KCNJ11 INS-IGF2 INS
12 diabetes mellitus 29.2 SLC19A2 PTF1A PDX1 KCNJ11 INS-IGF2 INS
13 pancreatic and cerebellar agenesis 11.9
14 transient neonatal diabetes mellitus 11.2
15 diabetes mellitus, insulin-dependent, 2 10.6 INS-IGF2 INS
16 cardiomyopathy, dilated, 1o 10.6 KCNJ11 ABCC8
17 type 1 diabetes mellitus 2 10.6 INS-IGF2 INS
18 hirata disease 10.5 INS ABCC8
19 munchausen by proxy 10.5 KCNJ11 GCK ABCC8
20 maturity-onset diabetes of the young, type 14 10.5 GCK ABCC8
21 acute insulin response 10.5 KCNJ11 INS ABCC8
22 segawa syndrome, autosomal recessive 10.5 INS-IGF2 INS
23 diabetes mellitus, transient neonatal, 1 10.5 KCNJ11 INS ABCC8
24 insulinomatosis and diabetes mellitus 10.4 INS ABCC8
25 maturity-onset diabetes of the young, type 3 10.4 PDX1 INS GCK
26 maturity-onset diabetes of the young, type 6 10.4 PDX1 INS GCK
27 maturity-onset diabetes of the young, type 7 10.4 PDX1 INS GCK
28 maturity-onset diabetes of the young, type 13 10.4 KCNJ11 INS GCK ABCC8
29 endocrine pancreas disease 10.4 KCNJ11 INS GCK ABCC8
30 pancreas disease 10.3 PTF1A KCNJ11 INS ABCC8
31 hyperinsulinemic hypoglycemia 10.3 KCNJ11 INS GCK ABCC8
32 glucose metabolism disease 10.3 KCNJ11 INS GCK ABCC8
33 hyperproinsulinemia 10.3 INS-IGF2 INS
34 epilepsy 10.3
35 acquired metabolic disease 10.3 KCNJ11 INS GCK ABCC8
36 hyperinsulinism 10.3 KCNJ11 INS GCK ABCC8
37 diabetes mellitus, ketosis-prone 10.3
38 thiamine-responsive megaloblastic anemia syndrome 10.3 SLC19A2 KCNJ11 INS ABCC8
39 fanconi-bickel syndrome 10.3 INS ABCC8
40 insulinoma 10.3 PDX1 INS GCK ABCC8
41 maturity-onset diabetes of the young, type 10 10.2 KCNJ11 INS-IGF2 INS GLIS3
42 autosomal recessive disease 10.2
43 glucose intolerance 10.2
44 exocrine pancreatic insufficiency 10.1
45 hypothyroidism 10.1
46 west syndrome 10.1
47 aspiration pneumonia 10.1
48 visual epilepsy 10.1
49 encephalopathy 10.1
50 seizure disorder 10.1

Graphical network of the top 20 diseases related to Diabetes Mellitus, Permanent Neonatal:



Diseases related to Diabetes Mellitus, Permanent Neonatal

Symptoms & Phenotypes for Diabetes Mellitus, Permanent Neonatal

Human phenotypes related to Diabetes Mellitus, Permanent Neonatal:

59 32 (show top 50) (show all 58)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 hyperglycemia 59 32 obligate (100%) Obligate (100%),Very frequent (99-80%) HP:0003074
2 failure to thrive 59 32 hallmark (90%) Very frequent (99-80%) HP:0001508
3 dehydration 59 32 occasional (7.5%) Occasional (29-5%),Very frequent (99-80%) HP:0001944
4 weight loss 59 32 hallmark (90%) Very frequent (99-80%) HP:0001824
5 hypovolemia 59 32 hallmark (90%) Very frequent (99-80%) HP:0011106
6 glycosuria 59 32 hallmark (90%) Very frequent (99-80%) HP:0003076
7 reduced pancreatic beta cells 59 32 hallmark (90%) Very frequent (99-80%) HP:0006274
8 neonatal insulin-dependent diabetes mellitus 59 32 hallmark (90%) Very frequent (99-80%) HP:0000857
9 elevated hemoglobin a1c 59 32 hallmark (90%) Very frequent (99-80%) HP:0040217
10 seizures 59 32 frequent (33%) Frequent (79-30%) HP:0001250
11 muscle weakness 59 32 frequent (33%) Frequent (79-30%) HP:0001324
12 global developmental delay 59 32 frequent (33%) Frequent (79-30%) HP:0001263
13 retinopathy 59 32 frequent (33%) Frequent (79-30%) HP:0000488
14 generalized myoclonic seizures 59 32 frequent (33%) Frequent (79-30%) HP:0002123
15 intrauterine growth retardation 59 32 frequent (33%) Frequent (79-30%) HP:0001511
16 generalized tonic-clonic seizures 59 32 frequent (33%) Frequent (79-30%) HP:0002069
17 arthrogryposis multiplex congenita 59 32 frequent (33%) Frequent (79-30%) HP:0002804
18 motor delay 59 32 frequent (33%) Frequent (79-30%) HP:0001270
19 downturned corners of mouth 59 32 occasional (7.5%) Occasional (29-5%),Frequent (79-30%) HP:0002714
20 prominent metopic ridge 59 32 occasional (7.5%) Occasional (29-5%),Frequent (79-30%) HP:0005487
21 mild global developmental delay 59 32 frequent (33%) Frequent (79-30%) HP:0011342
22 abnormal heart morphology 59 32 frequent (33%) Frequent (79-30%) HP:0001627
23 ketonuria 59 32 frequent (33%) Frequent (79-30%) HP:0002919
24 muscular hypotonia of the trunk 59 32 frequent (33%) Frequent (79-30%) HP:0008936
25 bilateral ptosis 59 32 occasional (7.5%) Occasional (29-5%),Frequent (79-30%) HP:0001488
26 contractures of the joints of the lower limbs 59 32 frequent (33%) Frequent (79-30%) HP:0005750
27 microalbuminuria 59 32 frequent (33%) Frequent (79-30%) HP:0012594
28 ataxia 59 32 occasional (7.5%) Occasional (29-5%) HP:0001251
29 muscular hypotonia 59 32 occasional (7.5%) Occasional (29-5%) HP:0001252
30 hearing impairment 59 32 occasional (7.5%) Occasional (29-5%) HP:0000365
31 short nose 59 32 occasional (7.5%) Occasional (29-5%) HP:0003196
32 anteverted nares 59 32 occasional (7.5%) Occasional (29-5%) HP:0000463
33 renal tubular dysfunction 59 32 occasional (7.5%) Occasional (29-5%) HP:0000124
34 vomiting 59 32 occasional (7.5%) Occasional (29-5%) HP:0002013
35 intellectual disability, severe 59 32 occasional (7.5%) Occasional (29-5%) HP:0010864
36 long philtrum 59 32 occasional (7.5%) Occasional (29-5%) HP:0000343
37 peripheral neuropathy 59 32 occasional (7.5%) Occasional (29-5%) HP:0009830
38 apraxia 59 32 occasional (7.5%) Occasional (29-5%) HP:0002186
39 hypsarrhythmia 59 32 occasional (7.5%) Occasional (29-5%) HP:0002521
40 coma 59 32 occasional (7.5%) Occasional (29-5%) HP:0001259
41 peripheral axonal neuropathy 59 32 occasional (7.5%) Occasional (29-5%) HP:0003477
42 pancreatic hypoplasia 59 32 occasional (7.5%) Occasional (29-5%) HP:0002594
43 thickened ears 59 32 occasional (7.5%) Occasional (29-5%) HP:0009894
44 clinodactyly of the 4th finger 59 32 occasional (7.5%) Occasional (29-5%) HP:0040025
45 clinodactyly 32 HP:0030084
46 ptosis 32 HP:0000508
47 diabetes mellitus 32 HP:0000819
48 intellectual disability 59 Frequent (79-30%)
49 neurodevelopmental delay 59 Frequent (79-30%)
50 abnormality of the upper urinary tract 59 Occasional (29-5%)

Symptoms via clinical synopsis from OMIM:

57
Skeletal Hands:
clinodactyly

Endocrine Features:
diabetes mellitus

Muscle Soft Tissue:
muscle weakness

Growth Other:
intrauterine growth retardation
postnatal growth catch-up occurs in treated patients without neurologic abnormalities

Abdomen Pancreas:
beta-cell dysfunction

Head And Neck Head:
prominent metopic suture

Head And Neck Mouth:
downturned mouth

Skeletal:
limb contractures

Immunology:
absence of pancreatic autoantibodies

Head And Neck Eyes:
ptosis

Neurologic Central Nervous System:
seizures
motor delay
hypsarrhythmia
developmental delay
axial hypotonia
more
Head And Neck Face:
long philtrum

Laboratory Abnormalities:
ketoacidosis
hyperglycemia

Head And Neck Nose:
anteverted nostrils
small, short nose

Growth Weight:
low birth weight

Head And Neck Ears:
thick ears

Neurologic Peripheral Nervous System:
diabetic peripheral neuropathy in long-standing cases

Clinical features from OMIM:

606176

UMLS symptoms related to Diabetes Mellitus, Permanent Neonatal:


seizures, muscle weakness

MGI Mouse Phenotypes related to Diabetes Mellitus, Permanent Neonatal:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 endocrine/exocrine gland MP:0005379 10.1 ABCC8 EIF2AK3 GCK GLIS3 INS KCNJ11
2 homeostasis/metabolism MP:0005376 10.1 ABCC8 EIF2AK3 GCK GLIS3 INS KCNJ11
3 digestive/alimentary MP:0005381 9.91 EIF2AK3 INS MNX1 PDX1 PTF1A SLC19A2
4 mortality/aging MP:0010768 9.73 EIF2AK3 GCK GLIS3 INS KCNJ11 MNX1
5 liver/biliary system MP:0005370 9.7 EIF2AK3 GCK INS PDX1 PPT1 PTF1A
6 no phenotypic analysis MP:0003012 9.23 ABCC8 EIF2AK3 GLIS3 INS KCNJ11 NKX6-1

Drugs & Therapeutics for Diabetes Mellitus, Permanent Neonatal

Drugs for Diabetes Mellitus, Permanent Neonatal (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 11)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Glyburide Approved Phase 4 10238-21-8 3488
2
Glucagon Approved Phase 4 16941-32-5
3 insulin Phase 4
4 Insulin, Globin Zinc Phase 4
5 Hypoglycemic Agents Phase 4
6 Glucagon-Like Peptide 1 Phase 4
7 Acidophilus Phase 1
8
Adenosine Approved, Investigational 58-61-7 60961
9 Antibodies
10 Immunoglobulins
11 Autoantibodies

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Long-term Sulfonylurea Response and Glucose Control After Switching From Insulin in Children With Diabetes Due to ABCC8 (SUR1) Mutations Unknown status NCT02624830 Phase 4 Sulfonylurea
2 Long-term Sulfonylurea Response and Glucose Control After Switching From Insulin in Children With Diabetes Due to KCNJ11 (KIR6.2) Mutations Completed NCT02624817 Phase 4 Sulfonylurea
3 Sulfonylureas in Neonatal Diabetes Mellitus With Mutations of 2 Type of Subunits Kir6.2 and SUR1 of the Pancreatic Beta-cell ATP-sensitive K+ Channel. Completed NCT00610038 Phase 2 glibenclamide
4 Study Evaluating the Optimal Dosage for Equivalence Between a Tablet and Capsule Dosage Form of an Intravaginal Treatment With Total Freeze-dried Culture of Lcr Regenerans® (Lactobacillus Rhamnosus Lcr35®) on Vaginal Flora Colonisation in Healthy Women. Completed NCT02730494 Phase 1
5 A Prospective Study of Sulfonylureas in Patients With Diabetes Due to Kir6.2 Mutations Completed NCT00334711 Sulfonylurea
6 Activating Mutation in the Gene Encoding the Adenosine Tri-phosphate Sensitive Potassium Channel Subunits (SUR 1, Kir 6.2) in Diabetic Patients Under the Age of One Year Not yet recruiting NCT03519217

Search NIH Clinical Center for Diabetes Mellitus, Permanent Neonatal

Genetic Tests for Diabetes Mellitus, Permanent Neonatal

Genetic tests related to Diabetes Mellitus, Permanent Neonatal:

# Genetic test Affiliating Genes
1 Permanent Neonatal Diabetes Mellitus 29 ABCC8 GCK INS KCNJ11 PDX1

Anatomical Context for Diabetes Mellitus, Permanent Neonatal

MalaCards organs/tissues related to Diabetes Mellitus, Permanent Neonatal:

41
Pancreas, Heart, Brain, Testes, Kidney, Pancreatic Islet, Eye

Publications for Diabetes Mellitus, Permanent Neonatal

Articles related to Diabetes Mellitus, Permanent Neonatal:

(show top 50) (show all 251)
# Title Authors PMID Year
1
KCNJ11 activating mutations in Italian patients with permanent neonatal diabetes. 38 4 8 71
15580558 2005
2
Heterozygous missense mutations in the insulin gene are linked to permanent diabetes appearing in the neonatal period or in early infancy: a report from the French ND (Neonatal Diabetes) Study Group. 4 8 71
18171712 2008
3
Insulin mutation screening in 1,044 patients with diabetes: mutations in the INS gene are a common cause of neonatal diabetes but a rare cause of diabetes diagnosed in childhood or adulthood. 4 8 71
18162506 2008
4
A novel mutation causing DEND syndrome: a treatable channelopathy of pancreas and brain. 4 8 71
17652641 2007
5
Insulin gene mutations as a cause of permanent neonatal diabetes. 4 8 71
17855560 2007
6
Activating mutations in the ABCC8 gene in neonatal diabetes mellitus. 4 8 71
16885549 2006
7
KCNJ11 activating mutations are associated with developmental delay, epilepsy and neonatal diabetes syndrome and other neurological features. 4 8 71
16670688 2006
8
A heterozygous activating mutation in the sulphonylurea receptor SUR1 (ABCC8) causes neonatal diabetes. 4 8 71
16613899 2006
9
Activating mutations in the gene encoding the ATP-sensitive potassium-channel subunit Kir6.2 and permanent neonatal diabetes. 4 8 71
15115830 2004
10
Neonatal diabetes mellitus due to complete glucokinase deficiency. 4 8 71
11372010 2001
11
Seven mutations in the human insulin gene linked to permanent neonatal/infancy-onset diabetes mellitus. 38 8 71
18451997 2008
12
Continued lessons from the INS gene: an intronic mutation causing diabetes through a novel mechanism. 8 71
26101329 2015
13
Interaction between mutations in the slide helix of Kir6.2 associated with neonatal diabetes and neurological symptoms. 8 71
20022885 2010
14
Prevalence of permanent neonatal diabetes in Slovakia and successful replacement of insulin with sulfonylurea therapy in KCNJ11 and ABCC8 mutation carriers. 38 4 8
17213273 2007
15
Molecular basis of Kir6.2 mutations associated with neonatal diabetes or neonatal diabetes plus neurological features. 38 4 71
15583126 2004
16
The G53D mutation in Kir6.2 (KCNJ11) is associated with neonatal diabetes and motor dysfunction in adulthood that is improved with sulfonylurea therapy. 4 71
18073297 2008
17
Permanent neonatal diabetes caused by dominant, recessive, or compound heterozygous SUR1 mutations with opposite functional effects. 4 71
17668386 2007
18
Origin of de novo KCNJ11 mutations and risk of neonatal diabetes for subsequent siblings. 4 8
17327377 2007
19
Switching from insulin to oral sulfonylureas in patients with diabetes due to Kir6.2 mutations. 4 8
16885550 2006
20
Transient neonatal diabetes mellitus is associated with a recurrent (R201H) KCNJ11 (KIR6.2) mutation. 4 71
16205880 2005
21
Permanent neonatal diabetes due to paternal germline mosaicism for an activating mutation of the KCNJ11 Gene encoding the Kir6.2 subunit of the beta-cell potassium adenosine triphosphate channel. 4 71
15292329 2004
22
Permanent Neonatal Diabetes Mellitus 38 71
20301620 2008
23
Glibenclamide treatment in permanent neonatal diabetes mellitus due to an activating mutation in Kir6.2. 38 8
15531505 2004
24
Recessive SLC19A2 mutations are a cause of neonatal diabetes mellitus in thiamine-responsive megaloblastic anaemia. 38 4
22369132 2012
25
Incidence of neonatal diabetes in Austria-calculation based on the Austrian Diabetes Register. 38 4
19496964 2010
26
Wolcott-Rallison syndrome is the most common genetic cause of permanent neonatal diabetes in consanguineous families. 38 4
19837917 2009
27
Diagnosis and treatment of neonatal diabetes: a United States experience. 38 4
18662362 2008
28
Permanent neonatal diabetes mellitus caused by a novel homozygous (T168A) glucokinase (GCK) mutation: initial response to oral sulphonylurea therapy. 38 4
18571549 2008
29
Mutations in the ABCC8 gene encoding the SUR1 subunit of the KATP channel cause transient neonatal diabetes, permanent neonatal diabetes or permanent diabetes diagnosed outside the neonatal period. 38 4
17919176 2007
30
Molecular basis of neonatal diabetes in Japanese patients. 8
17635943 2007
31
A mutation in the TMD0-L0 region of sulfonylurea receptor-1 (L225P) causes permanent neonatal diabetes mellitus (PNDM). 38 4
17317760 2007
32
An ATP-binding mutation (G334D) in KCNJ11 is associated with a sulfonylurea-insensitive form of developmental delay, epilepsy, and neonatal diabetes. 38 4
17259376 2007
33
Mutations in the genes encoding the pancreatic beta-cell KATP channel subunits Kir6.2 (KCNJ11) and SUR1 (ABCC8) in diabetes mellitus and hyperinsulinism. 71
16416420 2006
34
Mutations in PTF1A cause pancreatic and cerebellar agenesis. 38 4
15543146 2004
35
Neonatal diabetes mellitus and neonatal polycystic, dysplastic kidneys: Phenotypically discordant recurrence of a mutation in the hepatocyte nuclear factor-1beta gene due to germline mosaicism. 38 4
15181075 2004
36
Agenesis of human pancreas due to decreased half-life of insulin promoter factor 1. 38 4
12970316 2003
37
Molecular basis for Kir6.2 channel inhibition by adenine nucleotides. 71
12524280 2003
38
Neonatal diabetes mellitus: chromosomal analysis in transient and permanent cases. 38 4
12378186 2002
39
Complete glucokinase deficiency is not a common cause of permanent neonatal diabetes. 8
11942315 2002
40
Neonatal diabetes: new insights into aetiology and implications. 8
10895036 2000
41
Transient neonatal diabetes mellitus in a child with invdup(6)(q22q23) of paternal origin. 8
9450188 1997
42
Identification of 14 new glucokinase mutations and description of the clinical profile of 42 MODY-2 families. 71
9049484 1997
43
Isolated Pancreatic Aplasia Due to a Hypomorphic PTF1A Mutation. 4
27284104 2016
44
Successful transfer to sulfonylureas in KCNJ11 neonatal diabetes is determined by the mutation and duration of diabetes. 4
27033559 2016
45
13. Diabetes Care in the Hospital. 4
26696689 2016
46
11. Children and Adolescents. 4
26696687 2016
47
Age at the time of sulfonylurea initiation influences treatment outcomes in KCNJ11-related neonatal diabetes. 4
25877689 2015
48
ISPAD Clinical Practice Consensus Guidelines 2014. The diagnosis and management of monogenic diabetes in children and adolescents. 4
25182307 2014
49
GATA4 mutations are a cause of neonatal and childhood-onset diabetes. 4
24696446 2014
50
Microcephaly, epilepsy, and neonatal diabetes due to compound heterozygous mutations in IER3IP1: insights into the natural history of a rare disorder. 4
24138066 2014

Variations for Diabetes Mellitus, Permanent Neonatal

ClinVar genetic disease variations for Diabetes Mellitus, Permanent Neonatal:

6 (show top 50) (show all 258)
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 INS NM_000207.2(INS): c.-152C> A single nucleotide variant Pathogenic rs748749585 11:2182532-2182532 11:2161302-2161302
2 INS NM_000207.2(INS): c.-187_-164del deletion Pathogenic rs1135401727 11:2182544-2182567 11:2161314-2161337
3 GCK NM_000162.5(GCK): c.667G> A (p.Gly223Ser) single nucleotide variant Pathogenic rs1360415315 7:44189371-44189371 7:44149772-44149772
4 ABCC8 NM_000352.5(ABCC8): c.3593C> T (p.Pro1198Leu) single nucleotide variant Pathogenic rs1554909277 11:17424265-17424265 11:17402718-17402718
5 ABCC8 NM_000352.5(ABCC8): c.221G> A (p.Arg74Gln) single nucleotide variant Pathogenic rs72559734 11:17496502-17496502 11:17474955-17474955
6 INS NM_000207.2(INS): c.(?_-191)_(187_?)+1del deletion Pathogenic 11:2182014-2182571 11:2160784-2161341
7 INS NM_000207.3(INS): c.-39A> C single nucleotide variant Pathogenic rs1554921033 11:2182419-2182419 11:2161189-2161189
8 GCK NM_000162.5(GCK): c.790G> A (p.Gly264Ser) single nucleotide variant Pathogenic rs193929373 7:44187322-44187322 7:44147723-44147723
9 INS NM_000207.3(INS): c.127T> G (p.Cys43Gly) single nucleotide variant Pathogenic rs80356666 11:2182075-2182075 11:2160845-2160845
10 INS NM_000207.3(INS): c.140G> T (p.Gly47Val) single nucleotide variant Pathogenic rs80356667 11:2182062-2182062 11:2160832-2160832
11 INS NM_000207.3(INS): c.265C> T (p.Arg89Cys) single nucleotide variant Pathogenic rs80356669 11:2181150-2181150 11:2159920-2159920
12 INS NM_000207.3(INS): c.268G> T (p.Gly90Cys) single nucleotide variant Pathogenic rs80356670 11:2181147-2181147 11:2159917-2159917
13 INS NM_000207.3(INS): c.323A> G (p.Tyr108Cys) single nucleotide variant Pathogenic rs80356672 11:2181092-2181092 11:2159862-2159862
14 INS ; INS-IGF2 NM_000207.3(INS): c.94G> A (p.Gly32Ser) single nucleotide variant Pathogenic rs80356664 11:2182108-2182108 11:2160878-2160878
15 INS NM_000207.3(INS): c.94G> C (p.Gly32Arg) single nucleotide variant Pathogenic rs80356664 11:2182108-2182108 11:2160878-2160878
16 PDX1 NM_000209.4(PDX1): c.188del (p.Pro63fs) deletion Pathogenic rs193929377 13:28494463-28494463 13:27920326-27920326
17 ABCC8 NM_000352.5(ABCC8): c.257T> C (p.Val86Ala) single nucleotide variant Pathogenic rs193929360 11:17496466-17496466 11:17474919-17474919
18 ABCC8 NM_000352.5(ABCC8): c.394T> G (p.Phe132Val) single nucleotide variant Pathogenic rs80356637 11:17491666-17491666 11:17470119-17470119
19 ABCC8 NM_000352.5(ABCC8): c.404T> C (p.Leu135Pro) single nucleotide variant Pathogenic rs193929364 11:17491656-17491656 11:17470109-17470109
20 ABCC8 NM_000352.5(ABCC8): c.627C> A (p.Asp209Glu) single nucleotide variant Pathogenic rs80356640 11:17483325-17483325 11:17461778-17461778
21 ABCC8 NM_000352.5(ABCC8): c.631C> A (p.Gln211Lys) single nucleotide variant Pathogenic rs193929366 11:17483321-17483321 11:17461774-17461774
22 ABCC8 NM_000352.5(ABCC8): c.674T> C (p.Leu225Pro) single nucleotide variant Pathogenic rs1048095 11:17483278-17483278 11:17461731-17461731
23 KCNJ11 NM_000525.3(KCNJ11): c.1001G> A (p.Gly334Asp) single nucleotide variant Pathogenic rs193929358 11:17408638-17408638 11:17387091-17387091
24 KCNJ11 NM_000525.3(KCNJ11): c.103T> C (p.Phe35Leu) single nucleotide variant Pathogenic rs193929333 11:17409536-17409536 11:17387989-17387989
25 KCNJ11 NM_000525.3(KCNJ11): c.103T> G (p.Phe35Val) single nucleotide variant Pathogenic rs193929333 11:17409536-17409536 11:17387989-17387989
26 KCNJ11 NM_000525.3(KCNJ11): c.155A> G (p.Gln52Arg) single nucleotide variant Pathogenic rs193929337 11:17409484-17409484 11:17387937-17387937
27 KCNJ11 NM_000525.3(KCNJ11): c.497G> A (p.Cys166Tyr) single nucleotide variant Pathogenic rs80356618 11:17409142-17409142 11:17387595-17387595
28 KCNJ11 NM_000525.3(KCNJ11): c.544A> G (p.Ile182Val) single nucleotide variant Pathogenic rs193929348 11:17409095-17409095 11:17387548-17387548
29 KCNJ11 NM_000525.3(KCNJ11): c.602G> T (p.Arg201Leu) single nucleotide variant Pathogenic rs80356624 11:17409037-17409037 11:17387490-17387490
30 KCNJ11 NM_000525.3(KCNJ11): c.755T> C (p.Val252Ala) single nucleotide variant Pathogenic rs193929352 11:17408884-17408884 11:17387337-17387337
31 KCNJ11 NM_000525.3(KCNJ11): c.886A> C (p.Ile296Leu) single nucleotide variant Pathogenic rs193929353 11:17408753-17408753 11:17387206-17387206
32 KCNJ11 NM_000525.3(KCNJ11): c.886A> G (p.Ile296Val) single nucleotide variant Pathogenic rs193929353 11:17408753-17408753 11:17387206-17387206
33 KCNJ11 NM_000525.3(KCNJ11): c.964G> A (p.Glu322Lys) single nucleotide variant Pathogenic rs193929355 11:17408675-17408675 11:17387128-17387128
34 KCNJ11 NM_000525.3(KCNJ11): c.989A> G (p.Tyr330Cys) single nucleotide variant Pathogenic rs193929356 11:17408650-17408650 11:17387103-17387103
35 KCNJ11 NM_000525.3(KCNJ11): c.997T> A (p.Phe333Ile) single nucleotide variant Pathogenic rs193929357 11:17408642-17408642 11:17387095-17387095
36 PDX1 NM_000209.4(PDX1): c.533A> G (p.Glu178Gly) single nucleotide variant Pathogenic rs387906777 13:28498519-28498519 13:27924382-27924382
37 KCNJ11 NM_000525.3(KCNJ11): c.179T> A (p.Phe60Tyr) single nucleotide variant Pathogenic rs387906783 11:17409460-17409460 11:17387913-17387913
38 ABCC8 NM_000352.5(ABCC8): c.394T> C (p.Phe132Leu) single nucleotide variant Pathogenic rs80356637 11:17491666-17491666 11:17470119-17470119
39 ABCC8 NM_000352.5(ABCC8): c.638T> G (p.Leu213Arg) single nucleotide variant Pathogenic rs80356642 11:17483314-17483314 11:17461767-17461767
40 ABCC8 NM_000352.5(ABCC8): c.4270A> G (p.Ile1424Val) single nucleotide variant Pathogenic rs80356653 11:17417194-17417194 11:17395647-17395647
41 ABCC8 NM_000352.5(ABCC8): c.4135C> T (p.Arg1379Cys) single nucleotide variant Pathogenic rs137852673 11:17417462-17417462 11:17395915-17395915
42 ABCC8 NM_000352.5(ABCC8): c.215A> G (p.Asn72Ser) single nucleotide variant Pathogenic rs80356634 11:17496508-17496508 11:17474961-17474961
43 ABCC8 NM_000352.5(ABCC8): c.1144G> A (p.Glu382Lys) single nucleotide variant Pathogenic rs80356651 11:17474698-17474698 11:17453151-17453151
44 ABCC8 NM_000352.5(ABCC8): c.3554C> A (p.Ser1185Tyr) single nucleotide variant Pathogenic rs193929369 11:17426062-17426062 11:17404515-17404515
45 ABCC8 NM_000352.5(ABCC8): c.134C> T (p.Pro45Leu) single nucleotide variant Pathogenic rs267606623 11:17498190-17498190 11:17476643-17476643
46 ABCC8 NM_000352.5(ABCC8): c.257T> G (p.Val86Gly) single nucleotide variant Pathogenic rs193929360 11:17496466-17496466 11:17474919-17474919
47 INS NM_000207.3(INS): c.287G> A (p.Cys96Tyr) single nucleotide variant Pathogenic rs80356671 11:2181128-2181128 11:2159898-2159898
48 INS NM_000207.3(INS): c.71C> A (p.Ala24Asp) single nucleotide variant Pathogenic rs80356663 11:2182131-2182131 11:2160901-2160901
49 INS NM_000207.3(INS): c.143T> G (p.Phe48Cys) single nucleotide variant Pathogenic rs80356668 11:2182059-2182059 11:2160829-2160829
50 GCK NM_000162.5(GCK): c.683C> T (p.Thr228Met) single nucleotide variant Pathogenic rs80356655 7:44187429-44187429 7:44147830-44147830

UniProtKB/Swiss-Prot genetic disease variations for Diabetes Mellitus, Permanent Neonatal:

74 (show top 50) (show all 74)
# Symbol AA change Variation ID SNP ID
1 ABCC8 p.Phe132Leu VAR_029778 rs80356637
2 ABCC8 p.Leu213Arg VAR_029779 rs80356642
3 ABCC8 p.Ile1424Val VAR_029787 rs80356653
4 ABCC8 p.Val86Ala VAR_031354 rs193929360
5 ABCC8 p.Gly1400Arg VAR_031380 rs137852676
6 ABCC8 p.Pro45Leu VAR_072928 rs267606623
7 ABCC8 p.Asn72Ser VAR_072929 rs80356634
8 ABCC8 p.Val86Gly VAR_072930 rs193929360
9 ABCC8 p.Phe132Val VAR_072931 rs80356637
10 ABCC8 p.Pro207Ser VAR_072932
11 ABCC8 p.Glu208Lys VAR_072933
12 ABCC8 p.Asp209Glu VAR_072934 rs80356640
13 ABCC8 p.Gln211Lys VAR_072935 rs193929366
14 ABCC8 p.Leu225Pro VAR_072936 rs1048095
15 ABCC8 p.Thr229Ile VAR_072937 rs768017509
16 ABCC8 p.Tyr263Asp VAR_072938 rs778892038
17 ABCC8 p.Glu382Lys VAR_072939 rs80356651
18 ABCC8 p.Ala1184Glu VAR_072944 rs137852675
19 ABCC8 p.Glu1326Lys VAR_072945 rs200563930
20 ABCC8 p.Val1522Leu VAR_072953
21 GCK p.Thr228Met VAR_003705 rs80356655
22 GCK p.Gly261Arg VAR_003708 rs104894008
23 GCK p.Leu164Pro VAR_012350
24 GCK p.Met210Lys VAR_012351 rs80356654
25 GCK p.Glu40Lys VAR_079433 rs794727236
26 GCK p.Arg43Cys VAR_079434 rs148628002
27 GCK p.His50Asp VAR_079437
28 GCK p.Gly72Arg VAR_079440 rs193922289
29 GCK p.Ser151Thr VAR_079446
30 GCK p.Thr168Ala VAR_079448
31 GCK p.Lys169Arg VAR_079449
32 GCK p.Met393Thr VAR_079469
33 GCK p.Arg397Leu VAR_079470 rs193929375
34 GCK p.Ser441Leu VAR_079475 rs128680419
35 GCK p.Ala449Thr VAR_079476 rs193922282
36 INS p.Ala24Asp VAR_063723 rs80356663
37 INS p.His29Asp VAR_063724 rs121908272
38 INS p.Gly32Arg VAR_063725 rs80356664
39 INS p.Gly32Ser VAR_063726 rs80356664
40 INS p.Leu35Pro VAR_063727 rs121908273
41 INS p.Cys43Gly VAR_063728 rs80356666
42 INS p.Gly47Val VAR_063730 rs80356667
43 INS p.Phe48Cys VAR_063731 rs80356668
44 INS p.Arg89Cys VAR_063735 rs80356669
45 INS p.Gly90Cys VAR_063736 rs80356670
46 INS p.Cys96Ser VAR_063737 rs80356671
47 INS p.Cys96Tyr VAR_063738 rs80356671
48 INS p.Ser101Cys VAR_063739 rs121908276
49 INS p.Tyr103Cys VAR_063740 rs121908277
50 INS p.Tyr108Cys VAR_063741 rs80356672

Expression for Diabetes Mellitus, Permanent Neonatal

Search GEO for disease gene expression data for Diabetes Mellitus, Permanent Neonatal.

Pathways for Diabetes Mellitus, Permanent Neonatal

Pathways related to Diabetes Mellitus, Permanent Neonatal according to KEGG:

37
# Name Kegg Source Accession
1 Type II diabetes mellitus hsa04930
2 Maturity onset diabetes of the young hsa04950
3 Insulin signaling pathway hsa04910

GO Terms for Diabetes Mellitus, Permanent Neonatal

Cellular components related to Diabetes Mellitus, Permanent Neonatal according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 inward rectifying potassium channel GO:0008282 8.62 KCNJ11 ABCC8

Biological processes related to Diabetes Mellitus, Permanent Neonatal according to GeneCards Suite gene sharing:

(show all 15)
# Name GO ID Score Top Affiliating Genes
1 transcription by RNA polymerase II GO:0006366 9.84 STAT3 PDX1 NKX6-1 GLIS3
2 response to drug GO:0042493 9.83 STAT3 NKX6-1 KCNJ11 ABCC8
3 glucose homeostasis GO:0042593 9.67 STAT3 PDX1 INS GCK
4 glucose metabolic process GO:0006006 9.56 PDX1 KCNJ11 INS GCK
5 positive regulation of protein localization to nucleus GO:1900182 9.55 INS EIF2AK3
6 cellular glucose homeostasis GO:0001678 9.51 GCK ABCC8
7 pancreas development GO:0031016 9.5 PTF1A PDX1 NKX6-1
8 positive regulation of glycogen biosynthetic process GO:0045725 9.49 INS GCK
9 negative regulation of gluconeogenesis GO:0045721 9.48 INS GCK
10 cellular response to leptin stimulus GO:0044320 9.46 STAT3 GCK
11 endocrine pancreas development GO:0031018 9.46 PDX1 NKX6-1 MNX1 EIF2AK3
12 type B pancreatic cell differentiation GO:0003309 9.43 PDX1 NKX6-1
13 exocrine pancreas development GO:0031017 9.4 PTF1A PDX1
14 regulation of insulin secretion GO:0050796 9.35 SYT9 NKX6-1 KCNJ11 GCK ABCC8
15 detection of glucose GO:0051594 8.8 PDX1 NKX6-1 GCK

Molecular functions related to Diabetes Mellitus, Permanent Neonatal according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 sequence-specific DNA binding GO:0043565 9.35 STAT3 PTF1A PDX1 NKX6-1 MNX1
2 ATP-activated inward rectifier potassium channel activity GO:0015272 8.32 KCNJ11

Sources for Diabetes Mellitus, Permanent Neonatal

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
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57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 TGDB
71 Tocris
72 UMLS
73 UMLS via Orphanet
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