Insulin resistance (including lipodystrophy) (Version 1.17)

Description

Insulin resistance inclusion criteria (30562)
- Diagnosis of diabetes <25 years AND
- Not insulin dependent (>=3 years without insulin treatment) AND
- Non-obese (BMI <30) AND
- Acanthosis nigricans AND
- Biochemical confirmation of severe insulin resistance.

Insulin resistance exclusion criteria (30562)
- One or more pancreatic autoantibodies (GAD, IA2, ICA) positive (titre >99th
population centile)

Prior genetic testing guidance (30562)
- 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.

Closing statement (30562)
These requirements will be kept under continual review during the main programme and may be subject to change.

Insulin resistant prior genetic testing genes (30562)
Testing of the following genes should be carried out PRIOR TO RECRUITMENT where this is in line with current local practice: 
 - LMNA if partial lipodystrophy phenotype

Panel Activity

5 reviewers

Robert Semple (University of Cambridge)

Group: GeCIP domain
Workplace: Research lab
David Savage (IMS MRL, Uni. Cambridge)

Group: GeCIP domain
Workplace: Research lab
Sarah Leigh (Genomics England Curator)

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

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

Group: Other
Workplace: Other

26 Entities

26 reviewed, 15 green

List	Entity	Reviews	Mode of inheritance	Details
Filter Entities 26 Entitiess
Green Green List (high evidence)	AGPAT2	3 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen UKGTN Phenotypes Lipodystrophy, congenital generalized, type 1, 608594 Tags
Green Green List (high evidence)	ALMS1	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Illumina TruGenome Clinical Sequencing Services Literature Radboud University Medical Center, Nijmegen UKGTN Phenotypes Alstrom syndrome 203800 Tags
Green Green List (high evidence)	BLM	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Emory Genetics Laboratory Expert Review Green Illumina TruGenome Clinical Sequencing Services Literature Radboud University Medical Center, Nijmegen UKGTN Phenotypes Bloom syndrome, OMIM:210900 Tags
Green Green List (high evidence)	BSCL2	3 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen UKGTN Phenotypes Lipodystrophy, congenital generalized, type 2, OMIM:269700 Encephalopathy, progressive, with or without lipodystrophy, OMIM:615924 Tags
Green Green List (high evidence)	CAVIN1	4 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen Phenotypes Lipodystrophy, congenital generalized, type 4, 613327 Tags
Green Green List (high evidence)	INSR	3 reviews 2 green	BOTH monoallelic and biallelic, autosomal or pseudoautosomal	Sources Expert Review Green Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen UKGTN Phenotypes Diabetes mellitus, insulin-resistant, with acanthosis nigricans, 610549 Leprechaunism, 246200 Rabson-Mendenhall syndrome, 262190 Tags
Green Green List (high evidence)	LIPE	1 review 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert list Expert Review Green Tags
Green Green List (high evidence)	LMNA	3 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Eligibility statement prior genetic testing Expert Review Green Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen UKGTN Phenotypes Lipodystrophy, familial partial, 2, 151660 Tags
Green Green List (high evidence)	PCNT	3 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Emory Genetics Laboratory Expert Review Green Illumina TruGenome Clinical Sequencing Services Literature Radboud University Medical Center, Nijmegen UKGTN Phenotypes Microcephalic osteodysplastic primordial dwarfism, type II, OMIM:210720 Insulin resistance, HP:0000855 Tags
Green Green List (high evidence)	PCYT1A	3 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Literature Radboud University Medical Center, Nijmegen Phenotypes Spondylometaphyseal dysplasia with cone-rod dystrophy 608940 Tags
Green Green List (high evidence)	PIK3R1	3 reviews 2 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Green Literature UKGTN Phenotypes SHORT syndrome 269880 Tags
Green Green List (high evidence)	POLD1	3 reviews 2 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Green Radboud University Medical Center, Nijmegen Phenotypes Mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome, 615381 Tags
Green Green List (high evidence)	PPARG	3 reviews 2 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Green Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen UKGTN Phenotypes Insulin resistance, severe, digenic 604367 Lipodystrophy, familial partial, type 3 604367 Tags
Green Green List (high evidence)	WRN	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Emory Genetics Laboratory Expert Review Green Illumina TruGenome Clinical Sequencing Services Literature Radboud University Medical Center, Nijmegen Phenotypes Werner syndrome 277700 Tags
Green Green List (high evidence)	ZMPSTE24	3 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Radboud University Medical Center, Nijmegen Phenotypes Mandibuloacral dysplasia with type B lipodystrophy, 608612 Tags
Amber Amber List (moderate evidence)	PLIN1	4 reviews 2 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Amber Radboud University Medical Center, Nijmegen Phenotypes Lipodystrophy, familial partial, type 4, 613877 Tags
Red Red List (low evidence)	ADRA2A	1 review 1 red	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert list Phenotypes No OMIM number familial partial lipodystrophy Tags
Red Red List (low evidence)	AGPS	2 reviews 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Red Radboud University Medical Center, Nijmegen Phenotypes Lipodystrophy, congenital generalized, type 1, 608594 Tags
Red Red List (low evidence)	AKT2	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Emory Genetics Laboratory Expert Review Red Literature Radboud University Medical Center, Nijmegen Phenotypes Diabetes mellitus, type II, OMIM:125853 Type 2 diabetes mellitus, MONDO:0005148 Tags
Red Red List (low evidence)	CAV1	3 reviews 2 red	Not set	Sources Expert Review Red Radboud University Medical Center, Nijmegen Phenotypes Lipodystrophy, congenital generalized, type 3, 612526 Partial lipodystrophy, congenital cataracts, and neurodegeneration syndrome 606721 Tags
Red Red List (low evidence)	CIDEC	3 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Emory Genetics Laboratory Expert Review Red Literature Phenotypes Lipodystrophy, familial partial, type 5 615238 Tags
Red Red List (low evidence)	FGFR3	2 reviews 1 red	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Red Radboud University Medical Center, Nijmegen UKGTN Phenotypes Hypochondroplasia, 146000 Crouzon syndrome with acanthosis nigricans, 612247 Tags
Red Red List (low evidence)	NSMCE2	3 reviews 1 green 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Red Literature Phenotypes Dwarfism with extreme insulin resistance and acanthosis nigricans Tags
Red Red List (low evidence)	POC1A	2 reviews 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Red Literature Phenotypes Short stature, onychodysplasia, facial dysmorphism, and hypotrichosis 614813 Tags
Red Red List (low evidence)	PPP1R3A	3 reviews 2 red	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Red Radboud University Medical Center, Nijmegen Phenotypes Insulin resistance, severe, digenic 125853 Tags
Red Red List (low evidence)	PSMB8	3 reviews 2 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Red Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen Phenotypes Proteasome-associated autoinflammatory syndrome 1 and digenic forms, OMIM:256040 Autoinflammation, lipodystrophy, and dermatosis syndrome Tags

Insulin resistance (including lipodystrophy) (Version 1.17)

5 reviewers

26 Entities

26 reviewed, 15 green

3 reviews

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