Exome-first Approach Identified Novel Homozygous Dedicator of Cytokinesis 8 (DOCK8) Mutations in Three Unrelated Iranian Pedigrees Suspected with Hyper-IgE Syndrome.

The prevalence of primary immunodeficiency (PID) is rather high in Iran compared to the world average, mainly due to the high rate of consanguineous marriage. Despite that, little genetic information is available about primary immunodeficiencies in Iran. Autosomal recessive hyper IgE syndrome (AR-HIES) is a severe type of immunodeficiency, mainly caused by mutations in the dedicator of cytokinesis 8 (DOCK8). Rapid and precise diagnoses of patients suffering from AR-HIES can help to manage the patients and reach properly the treatment decision. However, in regions with low financial resources and limited expertise, deep phenotyping is uncommon. Therefore, an exome-first approach is helpful to make a genetic-based diagnosis. In the present study, whole-exome sequencing (WES) was applied to detect causative mutations in three unrelated primary immunodeficient patients with poor clinical information. One of the cases was a deceased patient with suspected hyper IgE syndrome (HIES) whose parents were subjected to WES. As a result, three novel pathogenic variants were detected in the DOCK8 gene, including two splicing sites (c.4241+1G>T and c.4886+1G>T) and one-stop-gain (c.4201G>T, p.Glu1401Ter) variants. Sanger sequencing confirmed the mutations' segregation in corresponding families. Further immunological investigations confirmed that HIES in the studied probands. The presence of frontal bossing and broad nose in one of the studied cases, in addition to the typical clinical presentation of DOCK8-AR-HIES, is notable. This work suggests that an exome-first approach can be a valuable alternative strategy for precise diagnosis of primary immunodeficiency patients.

Specific IgE Assay for Respiratory Allergens in Patients with Atopy in Ahvaz, Iran.

BACKGROUND: The frequency of sensitization to respiratory allergens is different in various geographical regions. OBJECTIVE: To determine the level of specific IgE to respiratory allergens in patients with atopy in Ahvaz, Iran. METHODS: In this retrospective cross-sectional study, the total and specific IgE data were recorded for 408 patients with allergic rhinitis and asthma referred to allergy diagnostic laboratory in Ahvaz from 2014 to 2017. The specific IgE was measured for nine respiratory allergens including Salsola kali, Triticum aestivum, Lolium perenne, Salix caprea, Prosopis juliflora, Dermatophagoides farinae, Aspergillus fumigatus, Alternaria alternate, Blatella germani using the ImmunoCAP system (Thermofisher-Phadia, Uppsala, Sweden) in referred patients. RESULTS: The median (IQR) age of participants was 15.5(27) years. The most common outdoor aeroallergens were Salsola kali (42.9%), Lolium perenne (32.2%), and Salix caprea (28.2%) while Dermatophagoides farina (21.1%) and Blatella germanica (20.6%) were the most dominant indoor sensitizers. Sensitization to at least one allergen was found in 57.4% of the patients. The prevalence of IgE sensitization to all respiratory allergens was higher in males. The prevalence of IgE sensitization to molds including Aspergillus fumigatus and Alternaria alternata significantly decreased with increased age. CONCLUSION: The pattern of allergen-specific IgE showed that Salsola Kali and Lolium perenne are the most common aeroallergens in allergic patients. This finding demonstrates the high frequency of IgE sensitization to outdoor allergens in the southwest of Iran.