PNDM4
MCID: DBT107
MIFTS: 29

Diabetes Mellitus, Permanent Neonatal, 4 (PNDM4)

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

Aliases & Classifications for Diabetes Mellitus, Permanent Neonatal, 4

MalaCards integrated aliases for Diabetes Mellitus, Permanent Neonatal, 4:

Name: Diabetes Mellitus, Permanent Neonatal, 4 57
Diabetes Mellitus, Permanent Neonatal 4 57 73
Permanent Neonatal Diabetes Mellitus 4 29 6
Pndm4 57 73

Characteristics:

OMIM®:

57 (Updated 05-Mar-2021)
Inheritance:
autosomal dominant
autosomal recessive (in 1 patient)

Miscellaneous:
germline mosaicism has been reported
median age of diagnosis 9-11 weeks (majority diagnosed before age 6 months)
homozygous mutations have been reported


HPO:

31
diabetes mellitus, permanent neonatal, 4:
Inheritance autosomal dominant inheritance autosomal recessive inheritance


Classifications:



External Ids:

OMIM® 57 618858
OMIM Phenotypic Series 57 PS606176
MeSH 44 D003920

Summaries for Diabetes Mellitus, Permanent Neonatal, 4

UniProtKB/Swiss-Prot : 73 Diabetes mellitus, permanent neonatal 4: A form of permanent neonatal diabetes mellitus, a type of diabetes characterized by onset of persistent hyperglycemia within the first six months of life. Initial clinical manifestations include intrauterine growth retardation, hyperglycemia, glycosuria, osmotic polyuria, severe dehydration, and failure to thrive. PNDM4 transmission pattern is consistent with autosomal dominant or autosomal recessive inheritance.

MalaCards based summary : Diabetes Mellitus, Permanent Neonatal, 4, also known as diabetes mellitus, permanent neonatal 4, is related to hyperproinsulinemia and maturity-onset diabetes of the young. An important gene associated with Diabetes Mellitus, Permanent Neonatal, 4 is INS (Insulin), and among its related pathways/superpathways are AMP-activated Protein Kinase (AMPK) Signaling and Type II diabetes mellitus. Related phenotypes are type i diabetes mellitus and small for gestational age

OMIM® : 57 Permanent neonatal diabetes mellitus-4 (PNDM4) is characterized by chronic hyperglycemia due to severe nonautoimmune insulin deficiency diagnosed in the first months of life (summary by Polak et al., 2008). For a discussion of genetic heterogeneity of permanent neonatal diabetes mellitus, see PNDM1 (606176). (618858) (Updated 05-Mar-2021)

Related Diseases for Diabetes Mellitus, Permanent Neonatal, 4

Graphical network of the top 20 diseases related to Diabetes Mellitus, Permanent Neonatal, 4:



Diseases related to Diabetes Mellitus, Permanent Neonatal, 4

Symptoms & Phenotypes for Diabetes Mellitus, Permanent Neonatal, 4

Human phenotypes related to Diabetes Mellitus, Permanent Neonatal, 4:

31 (show all 6)
# Description HPO Frequency HPO Source Accession
1 type i diabetes mellitus 31 HP:0100651
2 small for gestational age 31 HP:0001518
3 hyperglycemia 31 HP:0003074
4 elevated hemoglobin a1c 31 HP:0040217
5 diabetic ketoacidosis 31 HP:0001953
6 reduced c-peptide level 31 HP:0030795

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Mar-2021)
Growth Other:
failure to thrive
small for gestational age

Head And Neck Eyes:
retinopathy

Laboratory Abnormalities:
hyperglycemia
ketoacidosis
elevated hemoglobin a1c
ketosis
negative insulin autoantibodies
more
Neurologic Peripheral Nervous System:
neuropathy

Growth Weight:
reduced birth weight

Metabolic Features:
polydipsia

Skin Nails Hair Skin:
acanthosis nigricans

Genitourinary Kidneys:
polyuria

Endocrine Features:
neonatal diabetes mellitus

Cardiovascular Vascular:
diabetic macroangiopathy

Clinical features from OMIM®:

618858 (Updated 05-Mar-2021)

Drugs & Therapeutics for Diabetes Mellitus, Permanent Neonatal, 4

Search Clinical Trials , NIH Clinical Center for Diabetes Mellitus, Permanent Neonatal, 4

Genetic Tests for Diabetes Mellitus, Permanent Neonatal, 4

Genetic tests related to Diabetes Mellitus, Permanent Neonatal, 4:

# Genetic test Affiliating Genes
1 Permanent Neonatal Diabetes Mellitus 4 29 INS

Anatomical Context for Diabetes Mellitus, Permanent Neonatal, 4

Publications for Diabetes Mellitus, Permanent Neonatal, 4

Articles related to Diabetes Mellitus, Permanent Neonatal, 4:

# Title Authors PMID Year
1
Continued lessons from the INS gene: an intronic mutation causing diabetes through a novel mechanism. 57 6
26101329 2015
2
Seven mutations in the human insulin gene linked to permanent neonatal/infancy-onset diabetes mellitus. 57 6
18451997 2008
3
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. 57 6
18171712 2008
4
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. 57 6
18162506 2008
5
Insulin gene mutations as a cause of permanent neonatal diabetes. 6 57
17855560 2007

Variations for Diabetes Mellitus, Permanent Neonatal, 4

ClinVar genetic disease variations for Diabetes Mellitus, Permanent Neonatal, 4:

6
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 INS-IGF2 NM_000207.3(INS):c.187+241G>A SNV Pathogenic 268153 rs886041083 11:2181774-2181774 11:2160544-2160544
2 INS-IGF2 NM_000207.3(INS):c.94G>A (p.Gly32Ser) SNV Pathogenic 21122 rs80356664 11:2182108-2182108 11:2160878-2160878
3 INS-IGF2 NM_000207.3(INS):c.127T>G (p.Cys43Gly) SNV Pathogenic 21114 rs80356666 11:2182075-2182075 11:2160845-2160845
4 INS-IGF2 NM_000207.3(INS):c.265C>T (p.Arg89Cys) SNV Pathogenic 21117 rs80356669 11:2181150-2181150 11:2159920-2159920
5 INS-IGF2 NM_000207.3(INS):c.287G>A (p.Cys96Tyr) SNV Pathogenic 13387 rs80356671 11:2181128-2181128 11:2159898-2159898
6 INS-IGF2 NM_000207.3(INS):c.71C>A (p.Ala24Asp) SNV Pathogenic 13388 rs80356663 11:2182131-2182131 11:2160901-2160901
7 INS-IGF2 NM_000207.3(INS):c.143T>G (p.Phe48Cys) SNV Pathogenic 13389 rs80356668 11:2182059-2182059 11:2160829-2160829

UniProtKB/Swiss-Prot genetic disease variations for Diabetes Mellitus, Permanent Neonatal, 4:

73 (show all 15)
# Symbol AA change Variation ID SNP ID
1 INS p.Ala24Asp VAR_063723 rs80356663
2 INS p.His29Asp VAR_063724 rs121908272
3 INS p.Gly32Arg VAR_063725 rs80356664
4 INS p.Gly32Ser VAR_063726 rs80356664
5 INS p.Leu35Pro VAR_063727 rs121908273
6 INS p.Cys43Gly VAR_063728 rs80356666
7 INS p.Gly47Val VAR_063730 rs80356667
8 INS p.Phe48Cys VAR_063731 rs80356668
9 INS p.Arg89Cys VAR_063735 rs80356669
10 INS p.Gly90Cys VAR_063736 rs80356670
11 INS p.Cys96Ser VAR_063737 rs80356671
12 INS p.Cys96Tyr VAR_063738 rs80356671
13 INS p.Ser101Cys VAR_063739 rs121908276
14 INS p.Tyr103Cys VAR_063740 rs121908277
15 INS p.Tyr108Cys VAR_063741 rs80356672

Expression for Diabetes Mellitus, Permanent Neonatal, 4

Search GEO for disease gene expression data for Diabetes Mellitus, Permanent Neonatal, 4.

Pathways for Diabetes Mellitus, Permanent Neonatal, 4

Pathways related to Diabetes Mellitus, Permanent Neonatal, 4 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
11.41 INS-IGF2 INS
2
Show member pathways
10.61 INS-IGF2 INS

GO Terms for Diabetes Mellitus, Permanent Neonatal, 4

Molecular functions related to Diabetes Mellitus, Permanent Neonatal, 4 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 hormone activity GO:0005179 8.62 INS-IGF2 INS

Sources for Diabetes Mellitus, Permanent Neonatal, 4

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Mar-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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