TNDM1
MCID: DBT064
MIFTS: 31

Diabetes Mellitus, Transient Neonatal, 1 (TNDM1)

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

Aliases & Classifications for Diabetes Mellitus, Transient Neonatal, 1

MalaCards integrated aliases for Diabetes Mellitus, Transient Neonatal, 1:

Name: Diabetes Mellitus, Transient Neonatal, 1 57 73 13 71
6q24-Related Diabetes Mellitus 57 73 6
Tndm1 57 73
Diabetes Mellitus, Neonatal, Transient, Type 1 39
Diabetes Mellitus, Transient Neonatal 1 57
Transient Neonatal Diabetes Mellitus 71
Tndm 57
Dmtn 57

Characteristics:

OMIM®:

57 (Updated 05-Mar-2021)
Inheritance:
autosomal dominant (loss of maternal allele)

Miscellaneous:
imprinted disorder
usual resolution within 6 months
insulin therapy usually required


HPO:

31
diabetes mellitus, transient neonatal, 1:
Inheritance autosomal dominant inheritance


Classifications:



External Ids:

OMIM® 57 601410
MeSH 44 D003920
MedGen 41 C1832386
UMLS 71 C0342273 C1832386

Summaries for Diabetes Mellitus, Transient Neonatal, 1

OMIM® : 57 Neonatal diabetes mellitus (NDM), defined as insulin-requiring hyperglycemia within the first month 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 and resolves at a median age of 3 months, whereas the rest have a permanent form of diabetes (see PNDM1, 606176). In a significant number of patients with transient neonatal diabetes mellitus, type II diabetes appears later in life (Arthur et al., 1997). The major cause of transient neonatal diabetes (TND) is aberrant expression of imprinted genes at chromosome 6q24, associated in 20% of cases with DNA hypomethylation at the TND differentially methylated region (DMR), which lies within the imprinted promoter of the PLAGL1 gene (603044; Mackay et al., 2005). Over 50% of individuals with TND and hypomethylation at 6q24 also show mosaic DNA hypomethylation at other imprinted loci throughout the genome and a range of additional clinical features. (601410) (Updated 05-Mar-2021)

MalaCards based summary : Diabetes Mellitus, Transient Neonatal, 1, also known as 6q24-related diabetes mellitus, is related to diabetes mellitus, 6q24-related transient neonatal and transient neonatal diabetes mellitus. An important gene associated with Diabetes Mellitus, Transient Neonatal, 1 is ZFP57 (ZFP57 Zinc Finger Protein). Related phenotypes are dehydration and intrauterine growth retardation

UniProtKB/Swiss-Prot : 73 Diabetes mellitus, transient neonatal, 1: An autosomal dominant form of diabetes mellitus defined by the onset of mild-to-severe hyperglycemia within the first month of life. In about half of the neonates, diabetes is transient and resolves at a median age of 3 months, whereas the rest have a permanent form of diabetes.

Related Diseases for Diabetes Mellitus, Transient Neonatal, 1

Diseases in the Neonatal Diabetes family:

Diabetes Mellitus, Transient Neonatal, 1 Diabetes Mellitus, Transient Neonatal, 2
Diabetes Mellitus, Transient Neonatal, 3 Transient Neonatal Diabetes Mellitus
Diabetes Mellitus, 6q24-Related Transient Neonatal

Diseases related to Diabetes Mellitus, Transient Neonatal, 1 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 30)
# Related Disease Score Top Affiliating Genes
1 diabetes mellitus, 6q24-related transient neonatal 31.5 ZFP57 PLAGL1
2 transient neonatal diabetes mellitus 30.9 ZFP57 PLAGL1
3 permanent neonatal diabetes mellitus 30.7 ZFP57 PLAGL1
4 neonatal diabetes 29.7 ZFP57 PLAGL1
5 beckwith-wiedemann syndrome 29.0 ZFP57 PLAGL1
6 prostate cancer 11.2
7 malaria 11.1
8 hereditary spherocytosis 11.0
9 hypotrichosis 11.0
10 uniparental disomy of chromosome 6 10.9
11 paternal uniparental disomy of chromosome 6 10.9
12 diabetes mellitus, permanent neonatal, 1 10.9
13 macroglossia 10.9
14 anemia, congenital dyserythropoietic, type iv 10.9
15 patellar tendinitis 10.9
16 intermittent explosive disorder 10.9
17 hereditary elliptocytosis 10.9
18 trombiculiasis 10.9
19 maturity-onset diabetes of the young 10.1
20 diabetes mellitus 10.1
21 paternal uniparental disomy 10.1
22 colorectal cancer 10.0
23 hyperglycemia 9.9
24 monogenic diabetes 9.9
25 overgrowth syndrome 9.9
26 neuroblastoma 1 9.8
27 gestational trophoblastic neoplasm 9.7 ZFP57 PLAGL1
28 trophoblastic neoplasm 9.7 ZFP57 PLAGL1
29 chromosome 2q37 deletion syndrome 9.7 ZFP57 PLAGL1
30 silver-russell syndrome 1 9.7 ZFP57 PLAGL1

Graphical network of the top 20 diseases related to Diabetes Mellitus, Transient Neonatal, 1:



Diseases related to Diabetes Mellitus, Transient Neonatal, 1

Symptoms & Phenotypes for Diabetes Mellitus, Transient Neonatal, 1

Human phenotypes related to Diabetes Mellitus, Transient Neonatal, 1:

31
# Description HPO Frequency HPO Source Accession
1 dehydration 31 HP:0001944
2 intrauterine growth retardation 31 HP:0001511
3 hyperglycemia 31 HP:0003074
4 transient neonatal diabetes mellitus 31 HP:0008255
5 severe failure to thrive 31 HP:0001525

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Mar-2021)
Metabolic Features:
dehydration

Laboratory Abnormalities:
hyperglycemia

Growth Other:
intrauterine growth retardation
severe failure to thrive

Endocrine Features:
transient neonatal diabetes mellitus (tndm)
late predisposition to type 2 (insulin resistant) diabetes

Clinical features from OMIM®:

601410 (Updated 05-Mar-2021)

Drugs & Therapeutics for Diabetes Mellitus, Transient Neonatal, 1

Search Clinical Trials , NIH Clinical Center for Diabetes Mellitus, Transient Neonatal, 1

Genetic Tests for Diabetes Mellitus, Transient Neonatal, 1

Anatomical Context for Diabetes Mellitus, Transient Neonatal, 1

Publications for Diabetes Mellitus, Transient Neonatal, 1

Articles related to Diabetes Mellitus, Transient Neonatal, 1:

(show all 29)
# Title Authors PMID Year
1
Hypomethylation of multiple imprinted loci in individuals with transient neonatal diabetes is associated with mutations in ZFP57. 6 57
18622393 2008
2
Chromosome 6q24-related diabetes mellitus. 57
29662264 2018
3
Clinical characterisation of the multiple maternal hypomethylation syndrome in siblings. 6
18197189 2008
4
Molecular basis of neonatal diabetes in Japanese patients. 57
17635943 2007
5
Mutations in ATP-sensitive K+ channel genes cause transient neonatal diabetes and permanent diabetes in childhood or adulthood. 57
17446535 2007
6
Genetic and epigenetic defects at the 6q24 imprinted locus in a cohort of 13 patients with transient neonatal diabetes: new hypothesis raised by the finding of a unique case with hemizygotic deletion in the critical region. 57
16971482 2007
7
A maternal hypomethylation syndrome presenting as transient neonatal diabetes mellitus. 57
16816970 2006
8
Epimutation of the TNDM locus and the Beckwith-Wiedemann syndrome centromeric locus in individuals with transient neonatal diabetes mellitus. 57
16402210 2006
9
Monozygous triplets discordant for transient neonatal diabetes mellitus and for imprinting of the TNDM differentially methylated region. 57
15924231 2005
10
Bisulphite sequencing of the transient neonatal diabetes mellitus DMR facilitates a novel diagnostic test but reveals no methylation anomalies in patients of unknown aetiology. 57
15635480 2005
11
Impaired glucose homeostasis in transgenic mice expressing the human transient neonatal diabetes mellitus locus, TNDM. 57
15286800 2004
12
Transient neonatal diabetes, a disorder of imprinting. 57
12471198 2002
13
A conserved imprinting control region at the HYMAI/ZAC domain is implicated in transient neonatal diabetes mellitus. 57
11448939 2001
14
Partial paternal uniparental disomy of chromosome 6 in an infant with neonatal diabetes, macroglossia, and craniofacial abnormalities. 57
11038325 2000
15
An imprinted locus associated with transient neonatal diabetes mellitus. 57
10699182 2000
16
Variable features of transient neonatal diabetes mellitus with paternal isodisomy of chromosome 6. 57
10757646 2000
17
Neonatal diabetes: new insights into aetiology and implications. 57
10895036 2000
18
Localisation of a gene for transient neonatal diabetes mellitus to an 18.72 cR3000 (approximately 5.4 Mb) interval on chromosome 6q. 57
10204843 1999
19
Significance of genetic testing for paternal uniparental disomy of chromosome 6 in neonatal diabetes mellitus. 57
9880447 1999
20
Paternal uniparental disomy of chromosome 6 and transient neonatal diabetes mellitus. 57
9894800 1998
21
Transient neonatal diabetes mellitus in a child with invdup(6)(q22q23) of paternal origin. 57
9450188 1997
22
Growth effects of uniparental disomies and the conflict theory of genomic imprinting. 57
9385840 1997
23
Further evidence for an imprinted gene for neonatal diabetes localised to chromosome 6q22-q23. 57
8842729 1996
24
Transient neonatal diabetes mellitus in sibs. 57
5440211 1970
25
Genome-wide DNA methylation analysis of transient neonatal diabetes type 1 patients with mutations in ZFP57. 61
27075368 2016
26
Role of ZAC1 in transient neonatal diabetes mellitus and glucose metabolism. 61
26322169 2015
27
Genetic and epigenetic mutations affect the DNA binding capability of human ZFP57 in transient neonatal diabetes type 1. 61
23499433 2013
28
Transient neonatal diabetes, ZFP57, and hypomethylation of multiple imprinted loci: a detailed follow-up. 61
23150280 2013
29
Transient neonatal diabetes mellitus type 1. 61
20803656 2010

Variations for Diabetes Mellitus, Transient Neonatal, 1

ClinVar genetic disease variations for Diabetes Mellitus, Transient Neonatal, 1:

6 (show all 35)
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 ZFP57 NM_001109809.4(ZFP57):c.1383del (p.Tyr462fs) Deletion Pathogenic 717 rs606231122 6:29640505-29640505 6:29672728-29672728
2 ZFP57 NM_001109809.4(ZFP57):c.1372C>G (p.His458Asp) SNV Pathogenic 718 rs79020217 6:29640516-29640516 6:29672739-29672739
3 ZFP57 NM_001109809.4(ZFP57):c.743G>A (p.Arg248His) SNV Pathogenic 719 rs77625743 6:29641145-29641145 6:29673368-29673368
4 ZFP57 NM_001109809.4(ZFP57):c.829C>A (p.His277Asn) SNV Pathogenic 720 rs78378398 6:29641059-29641059 6:29673282-29673282
5 ZFP57 NM_001109809.4(ZFP57):c.898_905del (p.Gly299_Thr300insTer) Deletion Pathogenic 721 rs606231123 6:29640983-29640990 6:29673206-29673213
6 ZFP57 NM_001109809.4(ZFP57):c.313_314AG[2] (p.Glu106fs) Microsatellite Pathogenic 716 rs606231121 6:29643197-29643198 6:29675420-29675421
7 ZFP57 NM_001109809.2(ZFP57):c.783C>A (p.Cys261Ter) SNV Pathogenic 715 rs61730328 6:29641105-29641105 6:29673328-29673328
8 ZFP57 NM_001109809.5(ZFP57):c.1033G>C (p.Ala345Pro) SNV Uncertain significance 904449 6:29640855-29640855 6:29673078-29673078
9 ZFP57 NM_001109809.5(ZFP57):c.1230G>A (p.Pro410=) SNV Uncertain significance 907777 6:29640658-29640658 6:29672881-29672881
10 ZFP57 NM_001109809.5(ZFP57):c.826C>T (p.Arg276Cys) SNV Uncertain significance 904452 6:29641062-29641062 6:29673285-29673285
11 ZFP57 NM_001109809.4(ZFP57):c.724G>T (p.Asp242Tyr) SNV Uncertain significance 522540 rs1554211826 6:29641164-29641164 6:29673387-29673387
12 ZFP57 NM_001109809.4(ZFP57):c.495G>A (p.Val165=) SNV Uncertain significance 356217 rs771387494 6:29641393-29641393 6:29673616-29673616
13 ZFP57 NM_001109809.4(ZFP57):c.752G>A (p.Arg251His) SNV Uncertain significance 356214 rs774050037 6:29641136-29641136 6:29673359-29673359
14 ZFP57 NM_001109809.4(ZFP57):c.285C>T (p.Thr95=) SNV Uncertain significance 356220 rs373253380 6:29643230-29643230 6:29675453-29675453
15 ZFP57 NM_001109809.4(ZFP57):c.749G>A (p.Arg250His) SNV Uncertain significance 356215 rs199589695 6:29641139-29641139 6:29673362-29673362
16 ZFP57 NM_001109809.4(ZFP57):c.857C>T (p.Pro286Leu) SNV Uncertain significance 356212 rs753928819 6:29641031-29641031 6:29673254-29673254
17 ZFP57 NM_001109809.4(ZFP57):c.553A>G (p.Ser185Gly) SNV Uncertain significance 356216 rs755902229 6:29641335-29641335 6:29673558-29673558
18 ZFP57 NM_001109809.4(ZFP57):c.277C>G (p.Leu93Val) SNV Uncertain significance 356221 rs369213004 6:29643238-29643238 6:29675461-29675461
19 ZFP57 NM_001109809.4(ZFP57):c.798G>A (p.Lys266=) SNV Uncertain significance 356213 rs886061285 6:29641090-29641090 6:29673313-29673313
20 ZFP57 NM_001109809.5(ZFP57):c.843C>T (p.His281=) SNV Likely benign 904451 6:29641045-29641045 6:29673268-29673268
21 ZFP57 NM_001109809.5(ZFP57):c.732T>C (p.Ser244=) SNV Likely benign 905243 6:29641156-29641156 6:29673379-29673379
22 ZFP57 NM_001109809.4(ZFP57):c.1118C>G (p.Ser373Cys) SNV Likely benign 130769 rs193232883 6:29640770-29640770 6:29672993-29672993
23 ZFP57 NM_001109809.4(ZFP57):c.113G>A (p.Arg38Gln) SNV Likely benign 130770 rs142917604 6:29644668-29644668 6:29676891-29676891
24 ZFP57 NM_001109809.4(ZFP57):c.1086T>C (p.Thr362=) SNV Likely benign 130768 rs61730326 6:29640802-29640802 6:29673025-29673025
25 ZFP57 NM_001109809.5(ZFP57):c.532T>C (p.Tyr178His) SNV Likely benign 905244 6:29641356-29641356 6:29673579-29673579
26 ZFP57 NM_001109809.4(ZFP57):c.491G>A (p.Arg164Gln) SNV Likely benign 356218 rs200541066 6:29641397-29641397 6:29673620-29673620
27 ZFP57 NM_001109809.4(ZFP57):c.1472C>G (p.Thr491Ser) SNV Likely benign 356211 rs184974475 6:29640416-29640416 6:29672639-29672639
28 ZFP57 NM_001109809.4(ZFP57):c.475A>T (p.Thr159Ser) SNV Likely benign 356219 rs201703858 6:29641413-29641413 6:29673636-29673636
29 ZFP57 NM_001109809.4(ZFP57):c.593A>G (p.Asn198Ser) SNV Benign 130771 rs9461544 6:29641295-29641295 6:29673518-29673518
30 ZFP57 NM_001109809.4(ZFP57):c.112C>T (p.Arg38Trp) SNV Benign 356222 rs114772002 6:29644669-29644669 6:29676892-29676892
31 ZFP57 NM_001109809.5(ZFP57):c.937A>G (p.Arg313Gly) SNV Benign 904450 6:29640951-29640951 6:29673174-29673174
32 ZFP57 NM_001109809.4(ZFP57):c.559C>T (p.Arg187Cys) SNV Benign 130775 rs61730330 6:29641329-29641329 6:29673552-29673552
33 ZFP57 NM_001109809.4(ZFP57):c.1103A>T (p.Asp368Val) SNV Benign 130773 rs2535241 6:29640785-29640785 6:29673008-29673008
34 ZFP57 NM_001109809.4(ZFP57):c.783C>T (p.Cys261=) SNV Benign 130772 rs61730328 6:29641105-29641105 6:29673328-29673328
35 ZFP57 NM_001109809.4(ZFP57):c.374G>A (p.Arg125Gln) SNV Benign 130774 rs114591600 6:29641514-29641514 6:29673737-29673737

UniProtKB/Swiss-Prot genetic disease variations for Diabetes Mellitus, Transient Neonatal, 1:

73
# Symbol AA change Variation ID SNP ID
1 ZFP57 p.Arg166His VAR_054771 rs199589695
2 ZFP57 p.His193Asn VAR_054772 rs78378398
3 ZFP57 p.His374Asp VAR_054773 rs79020217

Expression for Diabetes Mellitus, Transient Neonatal, 1

Search GEO for disease gene expression data for Diabetes Mellitus, Transient Neonatal, 1.

Pathways for Diabetes Mellitus, Transient Neonatal, 1

GO Terms for Diabetes Mellitus, Transient Neonatal, 1

Molecular functions related to Diabetes Mellitus, Transient Neonatal, 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 RNA polymerase II regulatory region sequence-specific DNA binding GO:0000977 8.96 ZFP57 PLAGL1
2 DNA-binding transcription repressor activity, RNA polymerase II-specific GO:0001227 8.62 ZFP57 PLAGL1

Sources for Diabetes Mellitus, Transient Neonatal, 1

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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