title: Clinical, immunological and molecular characterization of DOCK8 and DOCK8-like deficient patients: single center experience of twenty-five patients.
abstract: OBJECTIVE
  Autosomal recessive hyper-IgE syndrome is a rare combined immunodeficiency characterized by susceptibility to viral infections, atopic eczema, high serum IgE and defective T cell activation. The genetic etiologies are diverse. Null mutations in DOCK8 and TYK2 are responsible for many cases. This study aims to provide a detailed clinical and immunological characterization of the disease and explore the underlying genetic defects among a large series of patients followed by a single center. The available data might improve our understanding of the disease pathogenesis and prognosis.
  
  
  METHODS
  Clinical data of twenty-five patients diagnosed with AR-HIES were collected. Seventeen patients screened for STAT3, TYK2 and DOCK8 mutations.
  
  
  RESULTS
  Sinopulmonary infections, dermatitis, hepatic disorders, cutaneous and systemic bacterial, fungal and viral infections were the most common clinical features. The rate of hepatic disorders and systemic infections were high. Twelve patients died with a median age of 10 years. CMV infection was the only statistically significant predicting factor for poor prognosis (early death). Three novel DOCK8 mutations and two large deletions were found in thirteen patients. No mutations found in STAT3 or TYK2 genes.
  
  
  CONCLUSIONS
  Autosomal recessive hyper-IgE syndrome is a combined immunodeficiency disease characterized by high morbidity and mortality rate. The different genetic background and environmental factors may explain the more severe phenotypes seen in our series. DOCK8 defect is the most common identified genetic cause. Patients with no identified genetic etiology are likely to carry mutations in the regulatory elements of genes tested or in novel genes that are yet to be discovered.
authors.affiliation: Pediatric Allergy and Clinical Immunology, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
authors.forename: Zobaida
authors.initials: Z
authors.lastname: Alsum
authors.forename: Abbas
authors.initials: A
authors.lastname: Hawwari
authors.forename: Osama
authors.initials: O
authors.lastname: Alsmadi
authors.forename: Safa
authors.initials: S
authors.lastname: Al-Hissi
authors.forename: Esteban
authors.initials: E
authors.lastname: Borrero
authors.forename: Asma'
authors.initials: A
authors.lastname: Abu-Staiteh
authors.forename: Hanif G
authors.initials: HG
authors.lastname: Khalak
authors.forename: Salma
authors.initials: S
authors.lastname: Wakil
authors.forename: Abdelmoneim M
authors.initials: AM
authors.lastname: Eldali
authors.forename: Rand
authors.initials: R
authors.lastname: Arnaout
authors.forename: Abdulaziz
authors.initials: A
authors.lastname: Al-Ghonaium
authors.forename: Saleh
authors.initials: S
authors.lastname: Al-Muhsen
authors.forename: Hasan
authors.initials: H
authors.lastname: Al-Dhekri
authors.forename: Bandar
authors.initials: B
authors.lastname: Al-Saud
authors.forename: Hamoud
authors.initials: H
authors.lastname: Al-Mousa
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D018389:Codon, Nonsense / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D005808:Genes, Recessive / Q000276:immunology; D020662:Guanine Nucleotide Exchange Factors / Q000737:chemistry* / Q000172:deficiency* / Q000235:genetics; D006782:Hospitals, Special; D006801:Humans; D007073:Immunoglobulin E / Q000009:adverse effects / Q000097:blood; D015994:Incidence; D007589:Job Syndrome / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology*; D008297:Male; D012529:Saudi Arabia / Q000453:epidemiology; D055502:Secondary Prevention
chemical_list: D018389:Codon, Nonsense; C516591:DOCK8 protein, human; D020662:Guanine Nucleotide Exchange Factors; D007073:Immunoglobulin E