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Interdisciplinary CompetenceMolecular Diagnostics
Know how in the analysis of genetic material.
For the benefit of patients.

IllnessHyper-IgE syndrome, differential diagnosis

Summary

Short information

Comprehensive differential diagnostic panel for Hyper-IgE syndrome containing 1 core gene, 4 core candidate genes and altogether 16 curated genes according to the clinical signs

ID
HP5599
Number of genes
15 Accredited laboratory test
Examined sequence length
14,9 kb (Core-/Core-canditate-Genes)
50,1 kb (Extended panel: incl. additional genes)
Analysis Duration
on request
Material
  • EDTA-anticoagulated blood (3-5 ml)
Diagnostic indications

NGS +

 

Gene panel

Selected genes

NameExon Length (bp)OMIM-GReferenz-Seq.Heredity
DCLRE1C2079NM_001033855.3AR
DOCK86300NM_203447.4AR
IL6R1407NM_000565.4AR
IL6ST2757NM_002184.4AR
STAT32313NM_139276.3AD
CARD113465NM_032415.7AD
CARD142223NM_001257970.1AD
FLG12186NM_002016.2AD
PGM31713NM_001199917.2AR
RAG13132NM_000448.3AR
RAG21584NM_000536.4AR
SPINK53285NM_001127698.2AR
TYK23564NM_003331.5AR
WAS1509NM_000377.3XLR
ZNF3412580NM_032819.5AR

Informations about the disease

Clinical Comment

Autosomal dominant hyper IgE syndrome (STAT-HIES; Job syndrome) caused by STAT3 mutations affects multiple body systems, especially the immune system with immunodeficiency. Recurrent infections such as pneumonia are common that form pneumatoceles. Skin infections and eczema are equally common. For unknown reasons, HIES patients have abnormally high blood levels of IgE. STAT-HIES also affects teeth and bones, the latter with hyperextensibility, scoliosis, osteopenia and a tendency to fracture. Deciduous teeth are retained. Other symptoms may include abnormalities of the coronary arteries, prominent facial features, and structural abnormalities of the brain, but these do not affect intelligence. In addition to STAT3, the most important genes to consider in the differential diagnosis are DOCK8, IL6R, IL6ST and TYK2, each of which follows an autosomal recessive inheritance pattern. A comprehensive differential diagnosis for high IgE levels includes additional genes: CARD11/-14, FLG, PGM3, RAG1/-2, SPINK5, WAS. The DNA diagnostic yield is not known. A negative molecular genetic result does not exclude the clinical diagnosis.

References: https://www.ncbi.nlm.nih.gov/books/NBK25507/

https://www.ncbi.nlm.nih.gov/books/NBK525947/

 

Synonyms
  • Alias: Job syndrome
  • Alias: STAT3 Loss-of-function hyper-IgE syndrome
  • Alias: STAT3 deficiency
  • Alias: STAT3-HIES
  • Alias: STAT3-deficient hyper-IgE syndrome
  • Allelic: A/B T-cell lymphopenia + G/D T-cell expans., severe cytomegalov. infect., autoimmun. (RAG1)
  • Allelic: Autoimmune disease, multisystem, infantile-onset, 1 (STAT3)
  • Allelic: B-cell expansion with NFKB and T-cell anergy (CARD11)
  • Allelic: Ichthyosis vulgaris (FLG)
  • Allelic: Immunodeficiency 11A (CARD11)
  • Allelic: Interleukin 6, serum level of, QTL (IL6R)
  • Allelic: Interleukin-6 receptor, soluble, serum level of, QTL (IL6R)
  • Allelic: Neutropenia, severe congenital, XL (WAS)
  • Allelic: Omenn syndrome (RAG1, RAG2)
  • Allelic: Severe combined immunodeficiency, B cell-negative (RAG1, RAg2)
  • Allelic: Thrombocytopenia, XL (WAS)
  • Allelic: Thrombocytopenia, XL, intermittent (WAS)
  • Combined cellular + humoral immune defects with granulomas (RAG1, RAG2)
  • Dermatitis, atopic, susceptibility to, 2 (FLG)
  • Hyper-IgE recurrent infection syndrome (STAT3)
  • Hyper-IgE recurrent infection syndrome 2, AR (DOCK8)
  • Hyper-IgE recurrent infection syndrome 3, AR (ZNF341)
  • Hyper-IgE recurrent infection syndrome 4, AR (IL6ST)
  • Hyper-IgE recurrent infection syndrome 5, AR (IL6R)
  • Immunodeficiency 11B with atopic dermatitis (CARD11)
  • Immunodeficiency 23 (PGM3)
  • Immunodeficiency 35 (TYK2)
  • Immunodysregulation, polyendocrinopathy + enteropathy, XL (FOXP3)
  • Netherton syndrome (SPINK5)
  • Omenn syndrome (DCLRE1C)
  • Pityriasis rubra pilaris (CARD14)
  • Psoriasis 2 (CARD14)
  • Severe combined immunodeficiency, Athabascan type (DCLRE1C)
  • Wiskott-Aldrich syndrome (WAS)
Heredity, heredity patterns etc.
  • AD
  • AR
  • XLR
OMIM-Ps
  • Multiple OMIM-Ps
ICD10 Code

Bioinformatics and clinical interpretation

No text defined