TNDM1
MCID: DBT064
MIFTS: 30

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 56 73 13 71
6q24-Related Diabetes Mellitus 56 73
Tndm1 56 73
Diabetes Mellitus, Neonatal, Transient, Type 1 39
Transient Neonatal Diabetes Mellitus 71
Tndm 56
Dmtn 56

Characteristics:

OMIM:

56
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 56 601410
MeSH 43 D003920
MedGen 41 C1832386
UMLS 71 C0342273 C1832386

Summaries for Diabetes Mellitus, Transient Neonatal, 1

OMIM : 56 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)

MalaCards based summary : Diabetes Mellitus, Transient Neonatal, 1, also known as 6q24-related diabetes mellitus, is related to neonatal diabetes mellitus and diabetes mellitus, 6q24-related transient neonatal. An important gene associated with Diabetes Mellitus, Transient Neonatal, 1 is ZFP57 (ZFP57 Zinc Finger Protein). Affiliated tissues include testes, and 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

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:

56
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

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

MalaCards organs/tissues related to Diabetes Mellitus, Transient Neonatal, 1:

40
Testes

Publications for Diabetes Mellitus, Transient Neonatal, 1

Articles related to Diabetes Mellitus, Transient Neonatal, 1:

(show all 30)
# Title Authors PMID Year
1
Hypomethylation of multiple imprinted loci in individuals with transient neonatal diabetes is associated with mutations in ZFP57. 6 56
18622393 2008
2
An imprinted locus associated with transient neonatal diabetes mellitus. 6 56
10699182 2000
3
Chromosome 6q24-related diabetes mellitus. 56
29662264 2018
4
Clinical characterisation of the multiple maternal hypomethylation syndrome in siblings. 6
18197189 2008
5
Molecular basis of neonatal diabetes in Japanese patients. 56
17635943 2007
6
Mutations in ATP-sensitive K+ channel genes cause transient neonatal diabetes and permanent diabetes in childhood or adulthood. 56
17446535 2007
7
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. 56
16971482 2007
8
A maternal hypomethylation syndrome presenting as transient neonatal diabetes mellitus. 56
16816970 2006
9
Epimutation of the TNDM locus and the Beckwith-Wiedemann syndrome centromeric locus in individuals with transient neonatal diabetes mellitus. 56
16402210 2006
10
Diabetes Mellitus, 6q24-Related Transient Neonatal 6
20301706 2005
11
Monozygous triplets discordant for transient neonatal diabetes mellitus and for imprinting of the TNDM differentially methylated region. 56
15924231 2005
12
Bisulphite sequencing of the transient neonatal diabetes mellitus DMR facilitates a novel diagnostic test but reveals no methylation anomalies in patients of unknown aetiology. 56
15635480 2005
13
Impaired glucose homeostasis in transgenic mice expressing the human transient neonatal diabetes mellitus locus, TNDM. 56
15286800 2004
14
Transient neonatal diabetes, a disorder of imprinting. 56
12471198 2002
15
A conserved imprinting control region at the HYMAI/ZAC domain is implicated in transient neonatal diabetes mellitus. 56
11448939 2001
16
Partial paternal uniparental disomy of chromosome 6 in an infant with neonatal diabetes, macroglossia, and craniofacial abnormalities. 56
11038325 2000
17
Variable features of transient neonatal diabetes mellitus with paternal isodisomy of chromosome 6. 56
10757646 2000
18
Neonatal diabetes: new insights into aetiology and implications. 56
10895036 2000
19
Localisation of a gene for transient neonatal diabetes mellitus to an 18.72 cR3000 (approximately 5.4 Mb) interval on chromosome 6q. 56
10204843 1999
20
Significance of genetic testing for paternal uniparental disomy of chromosome 6 in neonatal diabetes mellitus. 56
9880447 1999
21
Paternal uniparental disomy of chromosome 6 and transient neonatal diabetes mellitus. 56
9894800 1998
22
Transient neonatal diabetes mellitus in a child with invdup(6)(q22q23) of paternal origin. 56
9450188 1997
23
Growth effects of uniparental disomies and the conflict theory of genomic imprinting. 56
9385840 1997
24
Further evidence for an imprinted gene for neonatal diabetes localised to chromosome 6q22-q23. 56
8842729 1996
25
Transient neonatal diabetes mellitus in sibs. 56
5440211 1970
26
Genome-wide DNA methylation analysis of transient neonatal diabetes type 1 patients with mutations in ZFP57. 61
27075368 2016
27
Role of ZAC1 in transient neonatal diabetes mellitus and glucose metabolism. 61
26322169 2015
28
Genetic and epigenetic mutations affect the DNA binding capability of human ZFP57 in transient neonatal diabetes type 1. 61
23499433 2013
29
Transient neonatal diabetes, ZFP57, and hypomethylation of multiple imprinted loci: a detailed follow-up. 61
23150280 2013
30
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_001109809.2(ZFP57):c.783C>A (p.Cys261Ter)SNV Pathogenic 715 rs61730328 6:29641105-29641105 6:29673328-29673328
2 ZFP57 NM_001109809.4(ZFP57):c.313_314AG[2] (p.Glu106fs)short repeat Pathogenic 716 rs606231121 6:29643197-29643198 6:29675420-29675421
3 ZFP57 NM_001109809.4(ZFP57):c.1383del (p.Tyr462fs)deletion Pathogenic 717 rs606231122 6:29640505-29640505 6:29672728-29672728
4 ZFP57 NM_001109809.4(ZFP57):c.1372C>G (p.His458Asp)SNV Pathogenic 718 rs79020217 6:29640516-29640516 6:29672739-29672739
5 ZFP57 NM_001109809.4(ZFP57):c.743G>A (p.Arg248His)SNV Pathogenic 719 rs77625743 6:29641145-29641145 6:29673368-29673368
6 ZFP57 NM_001109809.4(ZFP57):c.829C>A (p.His277Asn)SNV Pathogenic 720 rs78378398 6:29641059-29641059 6:29673282-29673282
7 ZFP57 NM_001109809.4(ZFP57):c.898_905del (p.Gly299_Thr300insTer)deletion Pathogenic 721 rs606231123 6:29640983-29640990 6:29673206-29673213
8 ZFP57 NM_001109809.5(ZFP57):c.532T>C (p.Tyr178His)SNV Conflicting interpretations of pathogenicity 905244 rs146835830 6:29641356-29641356 6:29673579-29673579
9 ZFP57 NM_001109809.4(ZFP57):c.1118C>G (p.Ser373Cys)SNV Conflicting interpretations of pathogenicity 130769 rs193232883 6:29640770-29640770 6:29672993-29672993
10 ZFP57 NM_001109809.4(ZFP57):c.113G>A (p.Arg38Gln)SNV Conflicting interpretations of pathogenicity 130770 rs142917604 6:29644668-29644668 6:29676891-29676891
11 ZFP57 NM_001109809.4(ZFP57):c.1472C>G (p.Thr491Ser)SNV Conflicting interpretations of pathogenicity 356211 rs184974475 6:29640416-29640416 6:29672639-29672639
12 ZFP57 NM_001109809.4(ZFP57):c.475A>T (p.Thr159Ser)SNV Conflicting interpretations of pathogenicity 356219 rs201703858 6:29641413-29641413 6:29673636-29673636
13 ZFP57 NM_001109809.4(ZFP57):c.798G>A (p.Lys266=)SNV Uncertain significance 356213 rs886061285 6:29641090-29641090 6:29673313-29673313
14 ZFP57 NM_001109809.4(ZFP57):c.553A>G (p.Ser185Gly)SNV Uncertain significance 356216 rs755902229 6:29641335-29641335 6:29673558-29673558
15 ZFP57 NM_001109809.4(ZFP57):c.857C>T (p.Pro286Leu)SNV Uncertain significance 356212 rs753928819 6:29641031-29641031 6:29673254-29673254
16 ZFP57 NM_001109809.4(ZFP57):c.285C>T (p.Thr95=)SNV Uncertain significance 356220 rs373253380 6:29643230-29643230 6:29675453-29675453
17 ZFP57 NM_001109809.4(ZFP57):c.752G>A (p.Arg251His)SNV Uncertain significance 356214 rs774050037 6:29641136-29641136 6:29673359-29673359
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.749G>A (p.Arg250His)SNV Uncertain significance 356215 rs199589695 6:29641139-29641139 6:29673362-29673362
20 ZFP57 NM_001109809.4(ZFP57):c.495G>A (p.Val165=)SNV Uncertain significance 356217 rs771387494 6:29641393-29641393 6:29673616-29673616
21 ZFP57 NM_001109809.5(ZFP57):c.826C>T (p.Arg276Cys)SNV Uncertain significance 904452 6:29641062-29641062 6:29673285-29673285
22 ZFP57 NM_001109809.4(ZFP57):c.724G>T (p.Asp242Tyr)SNV Uncertain significance 522540 rs1554211826 6:29641164-29641164 6:29673387-29673387
23 ZFP57 NM_001109809.5(ZFP57):c.1230G>A (p.Pro410=)SNV Uncertain significance 907777 6:29640658-29640658 6:29672881-29672881
24 ZFP57 NM_001109809.5(ZFP57):c.1033G>C (p.Ala345Pro)SNV Uncertain significance 904449 rs200537697 6:29640855-29640855 6:29673078-29673078
25 ZFP57 NM_001109809.5(ZFP57):c.732T>C (p.Ser244=)SNV Likely benign 905243 6:29641156-29641156 6:29673379-29673379
26 ZFP57 NM_001109809.5(ZFP57):c.843C>T (p.His281=)SNV Likely benign 904451 6:29641045-29641045 6:29673268-29673268
27 ZFP57 NM_001109809.4(ZFP57):c.1086T>C (p.Thr362=)SNV Benign/Likely benign 130768 rs61730326 6:29640802-29640802 6:29673025-29673025
28 ZFP57 NM_001109809.4(ZFP57):c.491G>A (p.Arg164Gln)SNV Benign/Likely benign 356218 rs200541066 6:29641397-29641397 6:29673620-29673620
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.783C>T (p.Cys261=)SNV Benign 130772 rs61730328 6:29641105-29641105 6:29673328-29673328
31 ZFP57 NM_001109809.4(ZFP57):c.1103A>T (p.Asp368Val)SNV Benign 130773 rs2535241 6:29640785-29640785 6:29673008-29673008
32 ZFP57 NM_001109809.4(ZFP57):c.374G>A (p.Arg125Gln)SNV Benign 130774 rs114591600 6:29641514-29641514 6:29673737-29673737
33 ZFP57 NM_001109809.4(ZFP57):c.559C>T (p.Arg187Cys)SNV Benign 130775 rs61730330 6:29641329-29641329 6:29673552-29673552
34 ZFP57 NM_001109809.4(ZFP57):c.112C>T (p.Arg38Trp)SNV Benign 356222 rs114772002 6:29644669-29644669 6:29676892-29676892
35 ZFP57 NM_001109809.5(ZFP57):c.937A>G (p.Arg313Gly)SNV Benign 904450 rs61730327 6:29640951-29640951 6:29673174-29673174

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

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Pathways for Diabetes Mellitus, Transient Neonatal, 1

GO Terms for Diabetes Mellitus, Transient Neonatal, 1

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