Description
Severe multi-system atopic disease with high IgE (15085)

Severe multi-system atopic disease with high IgE inclusion criteria (29367)
- All of the following are required:
  - Adult patients only
  - Onset of patients' medical problems is in early childhood (often < 1 year old)
  - Severe persistent eczema (severe means requiring treatment over and above safe use of potent topical steroids, e.g. topical calcineurin inhibitors, UV light treatment or systemic immunosuppression: azathioprine, cyclosporine A, methotrexate, mycophenolate). Where topical calcineurin inhibitors are used as first line treatment and achieve good symptom control patients should only be included if serum IgE >10000.
  - Recurrent or chronic S. aureus skin infections, but this criterion may be absent if the patient is receiving systemic immunosuppressive treatment.
  - Asthma, but the severity can vary from mild to severe
  - High IgE levels >5000
  - Sensitised to a wide variety of aero-allergens and food allergens as measured by ImmunoCAP tests.

Severe multi-system atopic disease with high IgE exclusion criteria (29367)
- Those with systemic infections (unlike patients with classical hyper IgE syndrome)

Prior genetic testing guidance (29367)
- 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 (29367)
These requirements will be kept under continual review during the main programme and may be subject to change.

3 reviewers

  • Ellen McDonagh (Genomics England Curator)

    Group: other
    Workplace: other

  • William Rae (University Hospital Southampton NHS Foundation Trust)

    Group: NHS Genomic Medicine Centre
    Workplace: NHS clinical service

  • Ellen Thomas (Genomics England Curator)

    Group: Other
    Workplace: Other

8 genes

5 reviewed, 5 green

List Gene Reviews Mode of inheritance Details
8 genes
Green Green List (high evidence)
CARD11
1 review
1 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
Phenotypes
  • multisystem atopic disease, eczema, raised IgE, low IgM, eosinophilia
  • B-cell expansion with NFKB and T-cell anergy 616452 AD
Green Green List (high evidence)
DOCK8
1 review
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • UKGTN
  • Emory Genetics Laboratory
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Mental retardation, autosomal dominant 2, 614113Hyper-IgE recurrent infection syndrome, autosomal recessive, 243700
  • Hyper IgE syndromes
Green Green List (high evidence)
PGM3
1 review
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Literature
Phenotypes
  • Immunodeficiency 23
Green Green List (high evidence)
SPINK5
2 reviews
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Emory Genetics Laboratory
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Netherton syndrome, 256500Atopy, 147050
  • Netherton syndrome
Tags
  • gene-therapy-trial
Green Green List (high evidence)
STAT3
1 review
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Radboud University Medical Center, Nijmegen
  • UKGTN
  • Emory Genetics Laboratory
  • Illumina TruGenome Clinical Sequencing Services
  • Expert Review Green
Phenotypes
  • Hyper IgE Syndrome
  • Hyper IgE syndromes
  • Hyper-IgE recurrent infection syndrome, 147060
Red Red List (low evidence)
IL21R
0 reviews
Not set
Sources
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • [IgE, elevated level of], 147050Immunodeficiency, primary, autosomal recessive, IL21R-related, 615207
Red Red List (low evidence)
PLA2G7
0 reviews
Not set
Sources
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Platelet-activating factor acetylhydrolase deficiency, 614278{Asthma, susceptibility to}, 600807{Atopy, susceptibility to}, 147050
Red Red List (low evidence)
TYK2
0 reviews
Not set
Sources
  • Emory Genetics Laboratory
Phenotypes
  • Hyper IgE syndromes

0 STRs

0 reviewed, 0 green

List STR Reviews Mode of inheritance Details
0 STRss

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