Clinical, Immunological and Molecular Characterization of DOCK8 and DOCK8-like Deficient Patients: Single Center Experience of Twenty Five Patients
| Autor: | Esteban Borrero, Bandar Al-Saud, Asm’a Abu-Staiteh, Hasan Al-Dhekri, Abdelmoneim M. Eldali, Osama Alsmadi, Hanif Khalak, Saleh Al-Muhsen, Abbas Hawwari, Zobaida Alsum, Hamoud Al-Mousa, Safa Alhissi, Salma M. Wakil, Rand Arnaout, A. Al-Ghonaium |
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| Rok vydání: | 2012 |
| Předmět: |
Male
medicine.medical_specialty Adolescent Immunology Saudi Arabia Genes Recessive Disease Single Center Immunoglobulin E Hospitals Special Medical microbiology Secondary Prevention medicine Guanine Nucleotide Exchange Factors Humans Immunology and Allergy Child Immunodeficiency biology business.industry Incidence medicine.disease Codon Nonsense Tyrosine kinase 2 Child Preschool Etiology biology.protein Female Dock8 business Job Syndrome Gene Deletion |
| Zdroj: | Journal of Clinical Immunology. 33:55-67 |
| ISSN: | 1573-2592 0271-9142 |
| DOI: | 10.1007/s10875-012-9769-x |
| Popis: | 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.Clinical data of twenty-five patients diagnosed with AR-HIES were collected. Seventeen patients screened for STAT3, TYK2 and DOCK8 mutations.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.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. |
| Databáze: | OpenAIRE |
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