Repository of Research and Investigative Information

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دانشگاه علوم پزشکی و خدمات بهداشتی درمانی زنجان

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

(2020) Exome-first Approach Identified Novel Homozygous Dedicator of Cytokinesis 8 (DOCK8) Mutations in Three Unrelated Iranian Pedigrees Suspected with Hyper-IgE Syndrome. Iranian journal of allergy, asthma, and immunology. pp. 193-199. ISSN 1735-5249 (Electronic) & 1735-1502(Print)

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Abstract

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\textgreaterT and c.4886+1G\textgreaterT) and one-stop-gain (c.4201G\textgreaterT, 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.

Item Type: Article
Keywords: Dedicator of cytokinesis 8, Exome-first approach, Hyper IgE syndrome, Whole exome sequencing.
Subjects: QU Biochemistry. Cell Biology and Genetics > QU 300-560 Cell Biology and Genetics
Divisions: Education Vice-Chancellor Department > Faculty of Medicine > Department of Basic Science > Department of Molecular Medicine and Genetics
Page Range: pp. 193-199
Journal or Publication Title: Iranian journal of allergy, asthma, and immunology
Abstract and Indexing: ISI, Pubmed, Scopus, Other
Quartile : Q4
Volume: 19
Number: 2
Publisher: ProQuest
Identification Number: https://doi.org/10.18502/ijaai.v19i2.2772
ISSN: 1735-5249 (Electronic) & 1735-1502(Print)
Depositing User: خانم فائزه مظفری
URI: http://repository.zums.ac.ir/id/eprint/6845

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