Description
Neonatal diabetes inclusion criteria (30555)
- Neonatal diabetes diagnosed < 6 months
NOTE: diabetes diagnosed before 6 months of age almost universally has a
monogenic aetiology. Families should be recruited if diabetes is diagnosed
according to WHO criteria before the age of 6 months, and the diagnostic panel of
known genes is negative.

Neonatal diabetes exclusion criteria (30555)
- One or more pancreatic autoantibodies (GAD, IA2, ICA) positive (titre >99th population centile)

Prior genetic testing guidance (30555)
- Results should have been reviewed for all genetic tests undertaken, including disease-relevant genes in exome sequencing data. The patient is not eligible if they have a molecular diagnosis for their condition. 
- Genetic testing should continue according to routine local practice for this phenotype regardless of recruitment to the project; results of these tests must be submitted via the ‘Genetic investigations’ section of the data capture tool to allow comparison of WGS with current standard testing.  

PLEASE NOTE: The sensitivity of WGS compared to current diagnostic genetic testing has not yet been established. It is therefore important that tests which are clinically indicated under local standard practice continue to be carried out.

Neonatal diabetes prior genetic testing genes (30555)
Testing as below is strongly recommended PRIOR TO RECRUITMENT as WGS will not detect treatable mutations quickly enough to prevent irreversible neurological damage in a subset of patients:
Neonatal diabetes screen which is offered at the Exeter Molecular Genetics Laboratory or an equivalent genetic test.

Closing statement (30555)
These requirements will be kept under continual review during the main programme and may be subject to change.

4 reviewers

  • Sian Ellard (University of Exeter Medical School)

    Group: other
    Workplace: other

  • Rebecca Foulger (Genomics England curator)

    Group: Other
    Workplace: Other

  • Louise Daugherty (Genomics England Curator)

    Group: Other
    Workplace: Other

  • Elisa De Franco (University of Exeter Medical School)

    Group: Other
    Workplace: Research lab

30 Entities

29 reviewed, 27 green

List Entity Reviews Mode of inheritance Details
30 Entitiess
Green Green List (high evidence)
6q24 region (includes PLAGL1) Gain
ISCA-37442-Gain
Region
0 reviews
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • ClinGen
  • Expert Review Green
Phenotypes
  • 601410
  • Transient neonatal diabetes mellitus
  • Transient neonatal diabetes
Tags
Green Green List (high evidence)
ABCC8
2 reviews
1 green
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Eligibility statement prior genetic testing
  • Expert Review Green
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
  • UKGTN
Phenotypes
  • Hyperinsulinemic hypoglycemia, familial, 1, 256450
  • Hypoglycemia of infancy, leucine-sensitive, 240800
  • Diabetes mellitus, transient neonatal 2, 610374
  • Diabetes mellitus, noninsulin-dependent, 125853
  • Diabetes mellitus, permanent neonatal, 606176
  • Permanent Neonatal Diabetes Mellitus
  • Transient Neonatal Diabetes, Dominant
  • Permanent neonatal diabetes mellitus
  • transient neonatal diabetes (Dominant)
Tags
Green Green List (high evidence)
BSCL2
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review
  • Expert Review Green
Phenotypes
  • Congenital generalised lipodystrophy, severe insulin resistance and diabetes
Tags
Green Green List (high evidence)
EIF2AK3
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Eligibility statement prior genetic testing
  • Expert Review Green
  • UKGTN
Phenotypes
  • Wolcott-Rallison syndrome, 226980 (includes onset of diabetes in neonatal period/ early infancy)
Tags
Green Green List (high evidence)
FOXP3
2 reviews
1 green
X-LINKED: hemizygous mutation in males, biallelic mutations in females
Sources
  • Eligibility statement prior genetic testing
  • Expert Review Green
  • UKGTN
Phenotypes
  • Immunodysregulation, polyendocrinopathy, and enteropathy, X-linked, 304790 (includes Insulin-dependent diabetes mellitus (type I))
  • IPEX syndrome
Tags
Green Green List (high evidence)
GATA4
3 reviews
1 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Eligibility statement prior genetic testing
  • Expert Review Green
  • UKGTN
Phenotypes
  • Neonatal diabetes, Pancreatic agenesis and/or congenital heart defects
  • permanent neonatal diabetes melllitus
  • transient neonatal diabetes melllitus
Tags
  • deletions
Green Green List (high evidence)
GATA6
2 reviews
1 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Eligibility statement prior genetic testing
  • Expert Review Green
  • UKGTN
Phenotypes
  • Pancreatic agenesis and congenital heart defects, 600001
  • neonatal diabetes mellitus
Tags
  • mosaicism
Green Green List (high evidence)
GCK
3 reviews
1 green
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Eligibility statement prior genetic testing
  • Expert Review Green
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
  • UKGTN
Phenotypes
  • MODY, type II, 125851
  • Diabetes mellitus, noninsulin-dependent, late onset, 125853
  • Diabetes mellitus, gestational, 125851
  • Hyperinsulinemic hypoglycemia, familial, 3, 602485
  • Diabetes mellitus, permanent neonatal, 606176
  • Permanent Neonatal Diabetes Mellitus
  • Transient Neonatal Diabetes, Recessive
  • Permanent neonatal diabetes
Tags
Green Green List (high evidence)
GLIS3
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Eligibility statement prior genetic testing
  • Expert Review Green
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
  • UKGTN
Phenotypes
  • Diabetes mellitus, neonatal, with congenital hypothyroidism, 610199
  • Neonatal Diabetes mellitus with congenital hypothyroidism
Tags
Green Green List (high evidence)
HNF1B
3 reviews
1 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Eligibility statement prior genetic testing
  • Expert Review Green
  • UKGTN
Phenotypes
  • Transient neonatal diabetes
  • transient neonatal diabetes mellitus (TNDM)
  • permanent neonatal diabetes mellitus
  • Diabetes mellitus, noninsulin-dependent, 125853
Tags
  • mosaicism
Green Green List (high evidence)
IER3IP1
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Eligibility statement prior genetic testing
  • Expert Review Green
  • UKGTN
Phenotypes
  • Microcephaly, epilepsy and diabetes syndrome, 614231
  • neonatal diabetes
  • permanent neonatal diabetes
Tags
Green Green List (high evidence)
IL2RA
3 reviews
1 green 1 red
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review
  • Expert Review Green
Phenotypes
  • neonatal diabetes
  • insulin-dependent diabetes mellitus at 8-weeks
  • IPEX-like syndrome
  • {Diabetes, mellitus, insulin-dependent, susceptibility to, 10}, 601942
Tags
Green Green List (high evidence)
INS
2 reviews
1 green
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Eligibility statement prior genetic testing
  • Expert Review Green
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
  • UKGTN
Phenotypes
  • Hyperproinsulinemia, familial, with or without diabetes
  • Maturity-onset diabetes of the young, type 10, 613370
  • Diabetes mellitus, permanent neonatal, 606176
  • Diabetes mellitus, type 1, 125852
  • Diabetes mellitus, insulin-dependent, 2, 125852
  • Transient Neonatal Diabetes, Dominant/Recessive
  • Permanent Neonatal diabetes mellitus
Tags
Green Green List (high evidence)
INSR
1 review
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Other
Phenotypes
  • neonatal diabetes
Tags
Green Green List (high evidence)
KCNJ11
2 reviews
1 green
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Eligibility statement prior genetic testing
  • Expert Review Green
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
  • UKGTN
Phenotypes
  • Hyperinsulinemic hypoglycemia, familial, 2, 601820
  • Diabetes, permanent neonatal, 606176
  • Diabetes mellitus, permanent neonatal, with neurologic features, 606176
  • {Diabetes mellitus, type 2, susceptibility to}, 125853
  • Diabetes mellitus, transient neonatal, 3, 610582
  • Transient Neonatal Diabetes, Dominant
  • Diabetes Mellitus, PermanentNeonatal
  • Diabetes Mellitus, Transient Neonatal, 3
  • Transient Neonatal diabetes mellitus (Dominant)
Tags
Green Green List (high evidence)
LRBA
3 reviews
2 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review
  • Expert Review Green
Phenotypes
  • Immunodysregulation and type 1 diabetes
  • Immunodeficiency, common variable, 8, with autoimmunity, 614700
  • IPEX-like syndrome
Tags
Green Green List (high evidence)
MNX1
3 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Eligibility statement prior genetic testing
  • Expert Review Green
  • UKGTN
Phenotypes
  • Neonatal Diabetes
  • Permanent neonatal diabetes mellitus (PNDM)
Tags
Green Green List (high evidence)
NEUROD1
3 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Eligibility statement prior genetic testing
  • Expert Review Green
  • UKGTN
Phenotypes
  • Permanent neonatal diabetes and cerebellar agenesis
Tags
Green Green List (high evidence)
NEUROG3
3 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Eligibility statement prior genetic testing
  • Expert Review Green
  • UKGTN
Phenotypes
  • Permanent neonatal diabetes and enteric anendocrinosis
  • congenital malabsorptive diarrhea and neonatal diabetes
Tags
Green Green List (high evidence)
NKX2-2
3 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Eligibility statement prior genetic testing
  • Expert Review Green
  • UKGTN
Phenotypes
  • Neonatal diabetes
Tags
Green Green List (high evidence)
PDX1
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Eligibility statement prior genetic testing
  • Expert Review Green
  • UKGTN
Phenotypes
  • Permanent neonatal diabetes
  • pancreas agenesis
  • permanent neonatal diabetes mellitus associated with pancreas agenesis
  • Pancreatic agenesis 1, 260370
Tags
Green Green List (high evidence)
PTF1A
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Eligibility statement prior genetic testing
  • Expert Review Green
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
  • UKGTN
Phenotypes
  • Diabetes mellitus, permanent neonatal, with cerebellar agenesis, 609069
  • Permanent neonatal diabetes mellitus (PNDM)
  • Permanent neonatal diabetes with cerebellar agenesis
Tags
Green Green List (high evidence)
RFX6
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Eligibility statement prior genetic testing
  • Expert Review Green
  • UKGTN
Phenotypes
  • Neonatal diabetes, intestinal atresia and hepatobiliary abnormalities
  • Mitchell-Riley syndrome, 615710 (includes neonatal diabetes)
Tags
Green Green List (high evidence)
SLC19A2
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Eligibility statement prior genetic testing
  • Expert Review Green
  • UKGTN
Phenotypes
  • Thiamine-responsive megaloblastic anemia syndrome, 249270
  • neonatal diabetes mellitus in thiamine-responsive megaloblastic anaemia (TRMA)
  • permanent neonatal diabetes (PNDM)
Tags
Green Green List (high evidence)
SLC2A2
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Eligibility statement prior genetic testing
  • Expert Review Green
  • UKGTN
Phenotypes
  • Fanconi-Bickel syndrome, 227810
  • neonatal diabetes mellitus
  • transient neonatal diabetes mellitus (TNDM)
  • permanent neonatal diabetes (PDNM)
Tags
Green Green List (high evidence)
STAT3
3 reviews
1 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Eligibility statement prior genetic testing
  • Expert Review Green
  • UKGTN
Phenotypes
  • Neonatal diabetes and additional multi-organ autoimmunity
  • permanent neonatal diabetes
Tags
Green Green List (high evidence)
WFS1
2 reviews
1 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Other
Phenotypes
  • Syndromic neonatal diabetes
Tags
Green Green List (high evidence)
ZFP57
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Eligibility statement prior genetic testing
  • Expert Review Green
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
  • UKGTN
Phenotypes
  • Diabetes mellitus, transient neonatal, 1, 601410
  • Transient Neonatal Diabetes, Recessive
  • Transient Neonatal Diabetes
Tags
Red Red List (low evidence)
AGPAT2
4 reviews
1 green 2 red
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review
  • Expert Review Red
Phenotypes
  • neonatal diabetes mellitus
Tags
Red Red List (low evidence)
CISD2
2 reviews
1 red
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Red
  • Other
Tags

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