. DEFECTS OF ADAPTIVE IMMUNITY .

Hyper-IgE Syndrome (HIES) panel [14 genes]

There are two main forms of hyper-IgE syndromes (HIES) according to the gene defect and mode of inheritance: autosomal dominant (AD-HIES, or Job syndrome), mostly caused by mutations in the STAT3 gene, which is involved in the maturation of T cells, specifically Th17 cells; and the more severe autosomal recessive form (AR-HIES), which is usually explained by mutations in the DOCK8 gene, involved in B cell stimulation and in the maintenance of the structure and integrity of T cells and NK cells. However, mutations in other genes explain the less common forms of the disease.

Clinical features

  • Respiratory and skin infections
  • Eczema
  • Elevated IgE levels
  • Eosinophilia
  • Asthma, allergy, autoimmunity, immunodeficiency (AR-HIES)
  • Joint, osseous, dental problems (AD-HIES)
  • Onset: neonatal, infancy

Prevalence

  • 1:10,000 – 1:100,000 (AD-HIES)
  • 1:100,000-1:1,000,000 (AR-HIES)

Service benefits and management

  • Genetic diagnosis and counselling
  • Hematopoietic stem cell transplantation (HSCT)
  • Moisturizing creams
  • Antifungals
  • Antibiotic prophylaxis
  • IVIG therapy

ARPC1B, DOCK2, DOCK8, FOXP3, IL21R, PGM3, PHF11, SPINK5, STAT3, STK4, TYK2, WAS, WIPF1, ZNF341