TNDM1
MCID: DBT064
MIFTS: 36

Diabetes Mellitus, Transient Neonatal, 1 (TNDM1)

Categories: Endocrine diseases, Fetal diseases, Genetic diseases, Metabolic diseases, Rare diseases
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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 28 12 5 71
6q24-Related Diabetes Mellitus 57 73
Tndm1 57 73
Diabetes Mellitus, Transient Neonatal 1 57
Transient Neonatal Diabetes Mellitus 71
Tndm 57
Dmtn 57

Characteristics:


Inheritance:

Autosomal dominant 57

OMIM®:

57 (Updated 08-Dec-2022)
Miscellaneous:
imprinted disorder
usual resolution within 6 months
insulin therapy usually required
homozygous mutations in zfp57 alter the methylation status of the 6q24 imprinted locus


Classifications:



External Ids:

OMIM® 57 601410
MeSH 43 D003920
MedGen 40 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 08-Dec-2022)

MalaCards based summary: Diabetes Mellitus, Transient Neonatal, 1, also known as 6q24-related diabetes mellitus, is related to transient neonatal diabetes mellitus and maturity-onset diabetes of the young. An important gene associated with Diabetes Mellitus, Transient Neonatal, 1 is ZFP57 (ZFP57 Zinc Finger Protein). Affiliated tissues include cingulate cortex, skeletal muscle and pancreas, and related phenotypes are dehydration and intrauterine growth retardation

UniProtKB/Swiss-Prot: 73 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 33)
# Related Disease Score Top Affiliating Genes
1 transient neonatal diabetes mellitus 30.6 ZFP57 PLAGL1 HYMAI
2 maturity-onset diabetes of the young 29.6 ZFP57 HYMAI
3 paternal uniparental disomy of chromosome 6 29.5 PLAGL1 HYMAI
4 diabetes mellitus 29.4 ZFP57 PLAGL1 HYMAI
5 neonatal diabetes 29.4 ZFP57 PLAGL1 HYMAI
6 beckwith-wiedemann syndrome 28.9 ZFP57 PLAGL1 HYMAI
7 prostate cancer 11.2
8 malaria 11.2
9 hypotrichosis 11.2
10 hereditary spherocytosis 11.1
11 hemolytic anemia 11.1
12 diabetes mellitus, permanent neonatal, 1 11.0
13 macroglossia 10.9
14 anemia, congenital dyserythropoietic, type iiia 10.9
15 hereditary elliptocytosis 10.9
16 diabetes mellitus, 6q24-related transient neonatal 10.1
17 paternal uniparental disomy 10.1
18 colorectal cancer 10.0
19 prediabetes syndrome 9.9
20 hyperglycemia 9.9
21 monogenic diabetes 9.9
22 uniparental disomy of chromosome 6 9.9
23 overgrowth syndrome 9.9
24 neuroblastoma 1 9.8
25 intellectual developmental disorder, autosomal dominant 46 9.7 PLAGL1 HYMAI
26 temple syndrome 9.6 ZFP57 PLAGL1
27 kagami-ogata syndrome 9.6 ZFP57 PLAGL1
28 spastic paraplegia 17, autosomal dominant 9.6 ZFP57 PLAGL1
29 silver-russell syndrome 1 9.5 ZFP57 PLAGL1
30 umbilical hernia 9.5 ZFP57 PLAGL1 HYMAI
31 trophoblastic neoplasm 9.5 ZFP57 PLAGL1 HYMAI
32 gestational trophoblastic neoplasm 9.4 ZFP57 PLAGL1 HYMAI
33 permanent neonatal diabetes mellitus 9.4 ZFP57 PLAGL1 HYMAI

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:

30
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 dehydration 30 HP:0001944
2 intrauterine growth retardation 30 HP:0001511
3 severe failure to thrive 30 HP:0001525
4 hyperglycemia 30 HP:0003074
5 transient neonatal diabetes mellitus 30 HP:0008255

Symptoms via clinical synopsis from OMIM®:

57 (Updated 08-Dec-2022)
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 08-Dec-2022)

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

Genetic tests related to Diabetes Mellitus, Transient Neonatal, 1:

# Genetic test Affiliating Genes
1 Diabetes Mellitus, Transient Neonatal, 1 28 HYMAI ZFP57

Anatomical Context for Diabetes Mellitus, Transient Neonatal, 1

Organs/tissues related to Diabetes Mellitus, Transient Neonatal, 1:

MalaCards : Cingulate Cortex, Skeletal Muscle, Pancreas, Cortex, Breast, Brain

Publications for Diabetes Mellitus, Transient Neonatal, 1

Articles related to Diabetes Mellitus, Transient Neonatal, 1:

(show top 50) (show all 146)
# Title Authors PMID Year
1
Hypomethylation of multiple imprinted loci in individuals with transient neonatal diabetes is associated with mutations in ZFP57. 57 5
18622393 2008
2
Chromosome 6q24-related diabetes mellitus. 62 57
29662264 2018
3
Clinical characterisation of the multiple maternal hypomethylation syndrome in siblings. 62 5
18197189 2008
4
Molecular basis of neonatal diabetes in Japanese patients. 62 57
17635943 2007
5
Mutations in ATP-sensitive K+ channel genes cause transient neonatal diabetes and permanent diabetes in childhood or adulthood. 62 57
17446535 2007
6
A maternal hypomethylation syndrome presenting as transient neonatal diabetes mellitus. 62 57
16816970 2006
7
Epimutation of the TNDM locus and the Beckwith-Wiedemann syndrome centromeric locus in individuals with transient neonatal diabetes mellitus. 62 57
16402210 2006
8
Monozygous triplets discordant for transient neonatal diabetes mellitus and for imprinting of the TNDM differentially methylated region. 62 57
15924231 2005
9
Bisulphite sequencing of the transient neonatal diabetes mellitus DMR facilitates a novel diagnostic test but reveals no methylation anomalies in patients of unknown aetiology. 62 57
15635480 2005
10
Impaired glucose homeostasis in transgenic mice expressing the human transient neonatal diabetes mellitus locus, TNDM. 62 57
15286800 2004
11
A conserved imprinting control region at the HYMAI/ZAC domain is implicated in transient neonatal diabetes mellitus. 62 57
11448939 2001
12
An imprinted locus associated with transient neonatal diabetes mellitus. 62 57
10699182 2000
13
Variable features of transient neonatal diabetes mellitus with paternal isodisomy of chromosome 6. 62 57
10757646 2000
14
Neonatal diabetes: new insights into aetiology and implications. 62 57
10895036 2000
15
Localisation of a gene for transient neonatal diabetes mellitus to an 18.72 cR3000 (approximately 5.4 Mb) interval on chromosome 6q. 62 57
10204843 1999
16
Further evidence for an imprinted gene for neonatal diabetes localised to chromosome 6q22-q23. 62 57
8842729 1996
17
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
18
Transient neonatal diabetes, a disorder of imprinting. 57
12471198 2002
19
Partial paternal uniparental disomy of chromosome 6 in an infant with neonatal diabetes, macroglossia, and craniofacial abnormalities. 57
11038325 2000
20
Significance of genetic testing for paternal uniparental disomy of chromosome 6 in neonatal diabetes mellitus. 57
9880447 1999
21
Paternal uniparental disomy of chromosome 6 and transient neonatal diabetes mellitus. 57
9894800 1998
22
Growth effects of uniparental disomies and the conflict theory of genomic imprinting. 57
9385840 1997
23
Transient neonatal diabetes mellitus in a child with invdup(6)(q22q23) of paternal origin. 57
9450188 1997
24
Transient neonatal diabetes mellitus in sibs. 57
5440211 1970
25
Dematin inhibits glioblastoma malignancy through RhoA-mediated CDKs downregulation and cytoskeleton remodeling. 62
35561787 2022
26
Neonatal Diabetes Mellitus - Is Trisomy 21 Associated With Refractory Hyperglycaemia? 62
36414599 2022
27
Long-term follow-up of transient neonatal diabetes mellitus due to a novel homozygous c.7734C>T (p.R228C) mutation in ZFP57 gene: relapse at prepubertal age. 62
35218690 2022
28
The role of intermittent continuous glucose monitoring in a successful outpatient transition from insulin to glibenclamide in a patient with transient neonatal diabetes. 62
35612844 2022
29
Clinical characteristics, growth patterns, and long-term diabetes complications of 24 patients with neonatal diabetes mellitus: A single center experience. 62
34837310 2022
30
Genetic and clinical heterogeneity of permanent neonatal diabetes mellitus: a single tertiary centre experience. 62
34426871 2021
31
Developmental ethanol exposure causes central nervous system dysfunction and may slow the aging process in a Drosophila model of fetal alcohol spectrum disorder. 62
33961967 2021
32
Neonatal Diabetes Mellitus: Novel Mutations. 62
33409956 2021
33
8p21.3 deletions are rare causes of non-syndromic autism spectrum disorder. 62
33683518 2021
34
Differences between transient neonatal diabetes mellitus subtypes can guide diagnosis and therapy. 62
33606663 2021
35
Long-term Follow-up of Glycemic and Neurological Outcomes in an International Series of Patients With Sulfonylurea-Treated ABCC8 Permanent Neonatal Diabetes. 62
33184150 2021
36
Longitudinal Glycaemic Profiles during Remission in 6q24-Related Transient Neonatal Diabetes Mellitus. 62
34348302 2021
37
Transient Neonatal Diabetes Mellitus with the Rare Association of Nonsuppurative Sialadenitis and Genetic Defects in 6q24. 62
34422424 2021
38
Olfaction in Lamprey Pallium Revisited-Dual Projections of Mitral and Tufted Cells. 62
33406414 2021
39
Transient Neonatal Diabetes Mellitus in SHORT Syndrome: A Case Report. 62
34249805 2021
40
Congenital diabetes mellitus. 62
32274916 2020
41
Clinical features and partial proportional molecular genetics in neonatal diabetes mellitus: a retrospective analysis in southwestern China. 62
32279225 2020
42
Long-term Metabolic and Socioeducational Outcomes of Transient Neonatal Diabetes: A Longitudinal and Cross-sectional Study. 62
32273272 2020
43
MicroRNA-195 Functions as a Tumor Suppressor by Directly Targeting Fatty Acid Synthase in Malignant Meningioma. 62
31927122 2020
44
Relapsing 6q24-related transient neonatal diabetes mellitus with insulin resistance: A case report. 62
33088017 2020
45
Machine Learning Based Network Analysis Determined Clinically Relevant miRNAs in Breast Cancer. 62
33281885 2020
46
Phenotype of a transient neonatal diabetes point mutation (SUR1-R1183W) in mice. 62
34368464 2020
47
Severe Dental Disease as a Presenting Sign of Relapsed 6q24-Related Transient Neonatal Diabetes Mellitus. 62
33274084 2020
48
Clinical Characteristics, Molecular Features, and Long-Term Follow-Up of 15 Patients with Neonatal Diabetes: A Single-Centre Experience. 62
33498041 2020
49
Transient neonatal diabetes mellitus and hypomethylation at additional imprinted loci: novel ZFP57 mutation and review on the literature. 62
30315371 2019
50
Monogenic Forms of Diabetes Mellitus. 62
31588541 2019

Variations for Diabetes Mellitus, Transient Neonatal, 1

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

5 (show all 39)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 ZFP57 NM_001109809.5(ZFP57):c.317_318del (p.Glu106fs) MICROSAT Pathogenic
716 rs606231121 GRCh37: 6:29643197-29643198
GRCh38: 6:29675420-29675421
2 ZFP57 NM_001109809.5(ZFP57):c.1383del (p.Tyr462fs) DEL Pathogenic
717 rs606231122 GRCh37: 6:29640505-29640505
GRCh38: 6:29672728-29672728
3 ZFP57 NM_001109809.5(ZFP57):c.1372C>G (p.His458Asp) SNV Pathogenic
718 rs79020217 GRCh37: 6:29640516-29640516
GRCh38: 6:29672739-29672739
4 ZFP57 NM_001109809.5(ZFP57):c.743G>A (p.Arg248His) SNV Pathogenic
719 rs77625743 GRCh37: 6:29641145-29641145
GRCh38: 6:29673368-29673368
5 ZFP57 NM_001109809.5(ZFP57):c.829C>A (p.His277Asn) SNV Pathogenic
720 rs78378398 GRCh37: 6:29641059-29641059
GRCh38: 6:29673282-29673282
6 ZFP57 NM_001109809.5(ZFP57):c.898_905del (p.Gly299_Thr300insTer) DEL Pathogenic
721 rs606231123 GRCh37: 6:29640983-29640990
GRCh38: 6:29673206-29673213
7 ZFP57 NM_001109809.5(ZFP57):c.133del (p.Thr45fs) DEL Pathogenic
1323781 GRCh37: 6:29643827-29643827
GRCh38: 6:29676050-29676050
8 ZFP57 NM_001109809.2(ZFP57):c.783C>A (p.Cys261Ter) SNV Pathogenic
715 rs61730328 GRCh37: 6:29641105-29641105
GRCh38: 6:29673328-29673328
9 ZFP57 NM_001109809.5(ZFP57):c.711dup (p.Lys238fs) DUP Likely Pathogenic
1325370 GRCh37: 6:29641176-29641177
GRCh38: 6:29673399-29673400
10 ZFP57 NM_001109809.5(ZFP57):c.448C>T (p.Gln150Ter) SNV Likely Pathogenic
1325371 GRCh37: 6:29641440-29641440
GRCh38: 6:29673663-29673663
11 ZFP57 NM_001109809.5(ZFP57):c.277C>G (p.Leu93Val) SNV Uncertain Significance
356221 rs369213004 GRCh37: 6:29643238-29643238
GRCh38: 6:29675461-29675461
12 ZFP57 NM_001109809.5(ZFP57):c.1033G>C (p.Ala345Pro) SNV Uncertain Significance
904449 rs200537697 GRCh37: 6:29640855-29640855
GRCh38: 6:29673078-29673078
13 ZFP57 NM_001109809.5(ZFP57):c.495G>A (p.Val165=) SNV Uncertain Significance
356217 rs771387494 GRCh37: 6:29641393-29641393
GRCh38: 6:29673616-29673616
14 ZFP57 NM_001109809.5(ZFP57):c.752G>A (p.Arg251His) SNV Uncertain Significance
356214 rs774050037 GRCh37: 6:29641136-29641136
GRCh38: 6:29673359-29673359
15 ZFP57 NM_001109809.5(ZFP57):c.285C>T (p.Thr95=) SNV Uncertain Significance
356220 rs373253380 GRCh37: 6:29643230-29643230
GRCh38: 6:29675453-29675453
16 ZFP57 NM_001109809.5(ZFP57):c.749G>A (p.Arg250His) SNV Uncertain Significance
356215 rs199589695 GRCh37: 6:29641139-29641139
GRCh38: 6:29673362-29673362
17 ZFP57 NM_001109809.5(ZFP57):c.857C>T (p.Pro286Leu) SNV Uncertain Significance
356212 rs753928819 GRCh37: 6:29641031-29641031
GRCh38: 6:29673254-29673254
18 ZFP57 NM_001109809.5(ZFP57):c.553A>G (p.Ser185Gly) SNV Uncertain Significance
356216 rs755902229 GRCh37: 6:29641335-29641335
GRCh38: 6:29673558-29673558
19 ZFP57 NM_001109809.5(ZFP57):c.798G>A (p.Lys266=) SNV Uncertain Significance
356213 rs886061285 GRCh37: 6:29641090-29641090
GRCh38: 6:29673313-29673313
20 ZFP57 NM_001109809.5(ZFP57):c.724G>T (p.Asp242Tyr) SNV Uncertain Significance
522540 rs1554211826 GRCh37: 6:29641164-29641164
GRCh38: 6:29673387-29673387
21 ZFP57 NM_001109809.5(ZFP57):c.826C>T (p.Arg276Cys) SNV Uncertain Significance
904452 rs552912198 GRCh37: 6:29641062-29641062
GRCh38: 6:29673285-29673285
22 ZFP57 NM_001109809.5(ZFP57):c.1230G>A (p.Pro410=) SNV Uncertain Significance
907777 rs578187010 GRCh37: 6:29640658-29640658
GRCh38: 6:29672881-29672881
23 ZFP57 NM_001109809.5(ZFP57):c.843C>T (p.His281=) SNV Likely Benign
904451 rs141297510 GRCh37: 6:29641045-29641045
GRCh38: 6:29673268-29673268
24 ZFP57 NM_001109809.5(ZFP57):c.491G>A (p.Arg164Gln) SNV Likely Benign
356218 rs200541066 GRCh37: 6:29641397-29641397
GRCh38: 6:29673620-29673620
25 ZFP57 NM_001109809.5(ZFP57):c.1472C>G (p.Thr491Ser) SNV Likely Benign
356211 rs184974475 GRCh37: 6:29640416-29640416
GRCh38: 6:29672639-29672639
26 ZFP57 NM_001109809.5(ZFP57):c.475A>T (p.Thr159Ser) SNV Likely Benign
356219 rs201703858 GRCh37: 6:29641413-29641413
GRCh38: 6:29673636-29673636
27 ZFP57 NM_001109809.5(ZFP57):c.113G>A (p.Arg38Gln) SNV Likely Benign
130770 rs142917604 GRCh37: 6:29644668-29644668
GRCh38: 6:29676891-29676891
28 ZFP57 NM_001109809.5(ZFP57):c.1086T>C (p.Thr362=) SNV Likely Benign
130768 rs61730326 GRCh37: 6:29640802-29640802
GRCh38: 6:29673025-29673025
29 ZFP57 NM_001109809.5(ZFP57):c.732T>C (p.Ser244=) SNV Likely Benign
905243 rs190197921 GRCh37: 6:29641156-29641156
GRCh38: 6:29673379-29673379
30 ZFP57 NM_001109809.5(ZFP57):c.532T>C (p.Tyr178His) SNV Likely Benign
905244 rs146835830 GRCh37: 6:29641356-29641356
GRCh38: 6:29673579-29673579
31 ZFP57 NM_001109809.5(ZFP57):c.1118C>G (p.Ser373Cys) SNV Likely Benign
130769 rs193232883 GRCh37: 6:29640770-29640770
GRCh38: 6:29672993-29672993
32 ZFP57 NM_001109809.5(ZFP57):c.937A>G (p.Arg313Gly) SNV Benign
904450 rs61730327 GRCh37: 6:29640951-29640951
GRCh38: 6:29673174-29673174
33 ZFP57 NM_001109809.5(ZFP57):c.559C>T (p.Arg187Cys) SNV Benign
130775 rs61730330 GRCh37: 6:29641329-29641329
GRCh38: 6:29673552-29673552
34 ZFP57 NM_001109809.5(ZFP57):c.374G>A (p.Arg125Gln) SNV Benign
130774 rs114591600 GRCh37: 6:29641514-29641514
GRCh38: 6:29673737-29673737
35 ZFP57 NM_001109809.5(ZFP57):c.123+25G>A SNV Benign
1281971 GRCh37: 6:29644633-29644633
GRCh38: 6:29676856-29676856
36 ZFP57 NM_001109809.5(ZFP57):c.112C>T (p.Arg38Trp) SNV Benign
356222 rs114772002 GRCh37: 6:29644669-29644669
GRCh38: 6:29676892-29676892
37 ZFP57 NM_001109809.5(ZFP57):c.783C>T (p.Cys261=) SNV Benign
130772 rs61730328 GRCh37: 6:29641105-29641105
GRCh38: 6:29673328-29673328
38 ZFP57 NM_001109809.5(ZFP57):c.1103A>T (p.Asp368Val) SNV Benign
130773 rs2535241 GRCh37: 6:29640785-29640785
GRCh38: 6:29673008-29673008
39 ZFP57 NM_001109809.5(ZFP57):c.593A>G (p.Asn198Ser) SNV Benign
130771 rs9461544 GRCh37: 6:29641295-29641295
GRCh38: 6:29673518-29673518

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

Sources for Diabetes Mellitus, Transient Neonatal, 1

2 CDC
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56 OMIM via Orphanet
57 OMIM® (Updated 08-Dec-2022)
61 PubChem
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72 UMLS via Orphanet
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