Familial diabetes (Version 1.67)

Description

Diabetes inclusion criteria (29420)
- Diagnosis of diabetes <30 years of age
- Not insulin dependent (>=1 years without insulin treatment)
- Non-obese (BMI <30)

Unaffected family members should only be recruited if they have had testing to rule out diabetes (e.g. normal HbA1c) at or over the age of 40.

Diabetes exclusion criteria (29420)
- One or more autoantibodies positive

Prior genetic testing guidance (29420)
- 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.

Familial young-onset non-insulin-dependent diabetes prior genetic testing genes (29420)
Testing of the following genes should be carried out PRIOR TO RECRUITMENT where this is in line with current local practice:
No genes listed

Closing statement (29420)
These requirements will be kept under continual review during the main programme and may be subject to change.

Panel Activity

9 reviewers

Ellen McDonagh (Genomics England Curator)

Group: Other
Workplace: Other
Ellen Thomas (Genomics England)

Group: other
Workplace: other
Sian Ellard (University of Exeter Medical School)

Group: other
Workplace: other
Sarah Leigh (Genomics England Curator)

Group: Other
Workplace: Other
Louise Daugherty (Genomics England Curator)

Group: Other
Workplace: Other
Eleanor Williams (Genomics England Curator)

Group: Other
Workplace: Other
Ivone Leong (Genomics England Curator)

Group: Other
Workplace: Other
Jayne Houghton (Royal Devon and Exeter Foundation Trust)

Group: NHS Genomic Medicine Centre
Workplace: NHS diagnostic lab
Arina Puzriakova (Genomics England Curator)

Group: Other
Workplace: Other

57 Entities

56 reviewed, 50 green

List	Entity	Reviews	Mode of inheritance	Details
Filter Entities 57 Entitiess
Green Green List (high evidence)	ABCC8	3 reviews 2 green	BOTH monoallelic and biallelic, autosomal or pseudoautosomal	Sources Expert Review Green Illumina TruGenome Clinical Sequencing Services NHS GMS Radboud University Medical Center, Nijmegen UKGTN Phenotypes Permanent Neonatal Diabetes Mellitus Hyperinsulinemic hypoglycemia, familial, 1, 256450Hypoglycemia of infancy, leucine-sensitive, 240800Diabetes mellitus, transient neonatal 2, 610374Diabetes mellitus, noninsulin-dependent, 125853Diabetes mellitus, permanent neonatal, 6 Permanent Neonatal Diabetes Mellitus (recessive) Transient Neonatal Diabetes, Dominant Tags
Green Green List (high evidence)	AGPAT2	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Expert Review Green Tags
Green Green List (high evidence)	AKT2	1 review 1 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Green NHS GMS Phenotypes Diabetes mellitus, type II, OMIM:125853 Type 2 diabetes mellitus, MONDO:0005148 Tags
Green Green List (high evidence)	APPL1	1 review 1 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Green NHS GMS Phenotypes {Maturity-onset diabetes of the young, type 14}, 616511 Tags
Green Green List (high evidence)	BSCL2	3 reviews 1 green 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Expert Review Green Phenotypes Lipodystrophy, congenital generalized, type 2, OMIM:269700 Tags
Green Green List (high evidence)	CEL	4 reviews 2 green 1 red	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Green NHS GMS Radboud University Medical Center, Nijmegen Phenotypes Maturity-onset diabetes of the young, type VIII, 609812 Tags
Green Green List (high evidence)	CISD2	1 review 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green NHS GMS Phenotypes Wolfram syndrome 2, 604928 Tags
Green Green List (high evidence)	DCAF17	4 reviews 2 green 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Expert Review Green NHS GMS Phenotypes Woodhouse-Sakati syndrome, 241080 Tags
Green Green List (high evidence)	DNAJC3	1 review 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green NHS GMS Phenotypes ?Ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus, 616192 Tags
Green Green List (high evidence)	DYRK1B	1 review 1 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Green NHS GMS Phenotypes Abdominal obesity-metabolic syndrome 3, 615812 Tags
Green Green List (high evidence)	EIF2AK3	3 reviews 1 green 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Illumina TruGenome Clinical Sequencing Services UKGTN Phenotypes Multiple Epiphyseal Dysplasia with Early-Onset Diabetes Mellitus Wolcott-Rallison syndrome Tags
Green Green List (high evidence)	FOXP3	3 reviews 1 green 1 red	X-LINKED: hemizygous mutation in males, biallelic mutations in females	Sources Expert Review Green UKGTN Tags
Green Green List (high evidence)	GATA4	3 reviews 2 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Green NHS GMS UKGTN Tags
Green Green List (high evidence)	GATA6	3 reviews 2 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Green NHS GMS UKGTN Tags
Green Green List (high evidence)	GCK	4 reviews 3 green	BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal	Sources Emory Genetics Laboratory Expert Review Green Illumina TruGenome Clinical Sequencing Services NHS GMS Radboud University Medical Center, Nijmegen UKGTN Phenotypes Maturity-onset diabetes of the young (MODY) Maturity Onset Diabetes of the Young MODY, type II, 125851 Transient Neonatal Diabetes, Recessive Permanent Neonatal Diabetes Mellitus (recessive) Maturity Onset Diabetes of the Young (Dominant) Tags
Green Green List (high evidence)	GLIS3	2 reviews 1 green 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen UKGTN Phenotypes Diabetes Mellitus, Neonatal, with Congenital Hypothyroidism Diabetes mellitus, neonatal, with congenital hypothyroidism, 610199 -3 Tags
Green Green List (high evidence)	HNF1A	3 reviews 3 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Emory Genetics Laboratory Expert Review Green Illumina TruGenome Clinical Sequencing Services NHS GMS Radboud University Medical Center, Nijmegen UKGTN Phenotypes Diabetes mellitus, insulin-dependent, 20, OMIM:612520 {Diabetes mellitus, noninsulin-dependent, 2}, OMIM:125853 MODY, type III, OMIM:600496 Tags
Green Green List (high evidence)	HNF1B	4 reviews 3 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Green NHS GMS Radboud University Medical Center, Nijmegen UKGTN Phenotypes Renal cysts and diabetes syndrome, 137920 Tags
Green Green List (high evidence)	HNF4A	4 reviews 3 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Emory Genetics Laboratory Expert Review Green Illumina TruGenome Clinical Sequencing Services NHS GMS Radboud University Medical Center, Nijmegen UKGTN Phenotypes MODY, type I, 125850 Maturity Onset Diabetes of the Young OMIM 616026 Tags
Green Green List (high evidence)	IER3IP1	3 reviews 1 green 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green UKGTN Phenotypes Microcephaly, epilepsy, and diabetes syndrome Tags
Green Green List (high evidence)	INS	4 reviews 3 green	BOTH monoallelic and biallelic, autosomal or pseudoautosomal	Sources Expert Review Green Illumina TruGenome Clinical Sequencing Services NHS GMS Radboud University Medical Center, Nijmegen UKGTN Phenotypes Maturity Onset Diabetes of the Young Hyperproinsulinemia, familial, with or without diabetes Transient Neonatal Diabetes, Dominant/Recessive Maturity Onset Diabetes of the Young (Dominant) Tags
Green Green List (high evidence)	INSR	4 reviews 3 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Green NHS GMS UKGTN Phenotypes Diabetes mellitus, insulin-resistant, with acanthosis nigricans OMIM 610549 Tags
Green Green List (high evidence)	17q12 recurrent (RCAD syndrome) region (includes HNF1B) Loss ISCA-37432-Loss Region	1 review	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources ClinGen Expert Review Green Phenotypes RCAD syndrome utero-vaginal atresia Schizophrenia 614527 delayed development, intellectual disability Renal cysts and diabetes syndrome Autism Spectrum Disorder Mayer-Rokitansky-Kster-Hauser (MRKH) syndrome in females Chromosome 17q12 deletion syndrome global developmental delay Tags
Green Green List (high evidence)	KCNJ11	2 reviews 2 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Green Illumina TruGenome Clinical Sequencing Services NHS GMS Radboud University Medical Center, Nijmegen UKGTN Phenotypes Hyperinsulinemic hypoglycemia, familial, 2, 601820Diabetes, permanent neonatal, 606176Diabetes mellitus, permanent neonatal, with neurologic features, 606176{Diabetes mellitus, type 2, susceptibility to}, 125853Diabetes mellitus, transient neonatal, 3, 610582 Maturity Onset Diabetes of the Young Tags
Green Green List (high evidence)	LMNA	3 reviews 2 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Green NHS GMS UKGTN Tags
Green Green List (high evidence)	LRBA	3 reviews 1 green 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Expert Review Green Phenotypes Immunodeficiency, common variable, 8, with autoimmunity Tags
Green Green List (high evidence)	MNX1	3 reviews 1 green 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green UKGTN Tags
Green Green List (high evidence)	MT-TL1	3 reviews 2 green	MITOCHONDRIAL	Sources Expert Review Green NHS GMS UKGTN Phenotypes MELAS syndrome Tags gene-checked
Green Green List (high evidence)	NEUROD1	3 reviews 2 green	BOTH monoallelic and biallelic, autosomal or pseudoautosomal	Sources Expert Review Green Illumina TruGenome Clinical Sequencing Services NHS GMS Radboud University Medical Center, Nijmegen UKGTN Phenotypes Maturity Onset Diabetes of the Young {Diabetes mellitus, noninsulin-dependent}, 125853 Tags
Green Green List (high evidence)	NEUROG3	2 reviews 1 green 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green UKGTN Tags
Green Green List (high evidence)	NKX2-2	3 reviews 1 green 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Expert Review Removed UKGTN Tags gene-checked
Green Green List (high evidence)	PAX6	1 review 1 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Green NHS GMS Phenotypes Aniridia, 106210 diabetes Tags
Green Green List (high evidence)	PCBD1	5 reviews 2 green 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Expert Review Green NHS GMS Phenotypes Hyperphenylalaninemia, BH4-deficient, D 264070 Tags
Green Green List (high evidence)	PDX1	3 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Emory Genetics Laboratory Expert Review Green NHS GMS UKGTN Phenotypes Pancreatic agenesis 1 Tags
Green Green List (high evidence)	PIK3R1	3 reviews 2 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Expert Review Green NHS GMS Phenotypes Short stature, hyperextensibility of joints and/or inguinal hernia, ocular depression, Rieger anomaly, and teething delay (SHORT) syndrome Tags
Green Green List (high evidence)	PLIN1	6 reviews 4 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Expert Review Green NHS GMS Phenotypes Lipodystrophy, familial partial, type 4, OMIM:613877 Tags
Green Green List (high evidence)	POLD1	3 reviews 2 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Expert Review Green NHS GMS Phenotypes multisystem disorder that includes subcutaneous lipodystrophy, deafness, mandibular hypoplasia and hypogonadism in males Mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome Tags
Green Green List (high evidence)	PPARG	3 reviews 2 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Green Illumina TruGenome Clinical Sequencing Services NHS GMS UKGTN Phenotypes Diabetes Mellitus, Noninsulin-Dependent, with Acanthosis Nigricans and Hypertension Lipodystrophy, familial partial, type 3 Insulin resistance, severe, digenic Tags
Green Green List (high evidence)	PPP1R15B	1 review 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green NHS GMS Phenotypes Microcephaly, short stature, and impaired glucose metabolism 2, 616817 Tags
Green Green List (high evidence)	PTF1A	2 reviews 1 green 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen UKGTN Phenotypes Permanent neonatal diabetes mellitus (PNDM) Diabetes mellitus, permanent neonatal, with cerebellar agenesis, 609069 Tags
Green Green List (high evidence)	RFX6	3 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green NHS GMS UKGTN Phenotypes Mitchell-Riley syndrome Tags
Green Green List (high evidence)	SLC19A2	3 reviews 1 green 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green UKGTN Phenotypes Thiamine-responsive megaloblastic anemia syndrome MEGALOBLASTIC ANEMIA, THIAMINE-RESPONSIVE, WITH DIABETES MELLITUS AND SENSORINEURAL DEAFNESS ROGERS SYNDROME Tags
Green Green List (high evidence)	SLC29A3	3 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Expert Review Green NHS GMS Phenotypes Histiocytosis-lymphadenopathy plus syndrome, OMIM:602782 Pigmented hypertrichotic dermatosis with insulin-dependent diabetes (PHID) syndrome Tags
Green Green List (high evidence)	SLC2A2	3 reviews 1 green 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Radboud University Medical Center, Nijmegen UKGTN Phenotypes {Diabetes mellitus, noninsulin-dependent} Fanconi-Bickel syndrome Tags
Green Green List (high evidence)	STAT3	3 reviews 1 green 1 red	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Green UKGTN Tags
Green Green List (high evidence)	TRMT10A	3 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Expert Review Green NHS GMS Phenotypes young onset diabetes, short stature and microcephaly with intellectual disability failure to thrive and microcephaly, ketoacidosis at onset of diabetes and islet cell autoantibodies Tags
Green Green List (high evidence)	WFS1	5 reviews 2 green	BOTH monoallelic and biallelic, autosomal or pseudoautosomal	Sources Expert Review Green NHS GMS Radboud University Medical Center, Nijmegen Phenotypes Wolfram syndrome, OMIM:222300 Tags
Green Green List (high evidence)	ZBTB20	4 reviews 2 green 1 red	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Expert Review Green NHS GMS Phenotypes Primrose syndrome, 259050 Tags
Green Green List (high evidence)	ZFP57	2 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Illumina TruGenome Clinical Sequencing Services NHS GMS Radboud University Medical Center, Nijmegen UKGTN Phenotypes Transient Neonatal Diabetes, Recessive Diabetes mellitus, transient neonatal, 1, 601410 Tags
Green Green List (high evidence)	ZMPSTE24	0 reviews	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Phenotypes Mandibuloacral dysplasia with type B lipodystrophy, 608612 Tags
Red Red List (low evidence)	BLK	3 reviews 1 red	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Red Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen Phenotypes Maturity Onset Diabetes of the Young Maturity-onset diabetes of the young, type 11, 613375 Tags
Red Red List (low evidence)	IL2RA	3 reviews 2 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Expert Review Red Tags
Red Red List (low evidence)	KLF11	3 reviews 2 red	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Red Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen Phenotypes Maturity Onset Diabetes of the Young Maturity-onset diabetes of the young, type VII, 610508 Tags
Red Red List (low evidence)	LIPC	3 reviews 2 red	Not set	Sources Expert Review Red Radboud University Medical Center, Nijmegen Phenotypes [High density lipoprotein cholesterol level QTL 12], 612797 {Diabetes mellitus, noninsulin-dependent}, 125853 Hepatic lipase deficiency, 614025 Tags
Red Red List (low evidence)	PAX4	3 reviews 2 red	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Red Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen Phenotypes Maturity Onset Diabetes of the Young Maturity-onset diabetes of the young, type IX, 612225 Tags
Red Red List (low evidence)	STAT1	3 reviews 2 red	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Expert Review Red Tags
No list No list	ENPP1	3 reviews 2 red	Not set	Sources Expert Review Removed Radboud University Medical Center, Nijmegen Phenotypes Ossification of posterior longitudinal ligament of spine, 602475{Diabetes mellitus, non-insulin-dependent, susceptibility to}, 125853{Obesity, susceptibility to}, 601665Arterial calcification, generalized, of infancy, 1, 208000Hypophos Tags curated_removed

Major version comments

18/July/2016 - panel revised due to expert review and further evidence, and promoted to version 1.

Familial diabetes (Version 1.67)

9 reviewers

57 Entities

56 reviewed, 50 green

3 reviews

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Phenotypes

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2 reviews

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1 review

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3 reviews

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4 reviews

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2 reviews

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3 reviews

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4 reviews

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4 reviews

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3 reviews

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