Confirmation of Hyperimmunoglobulin E Syndrome in Two Patients with an Ocular Problem: Detection of Two New DOCK8 Mutations

Early diagnosis of primary immunodeficiencies is crucial for timely treatment and preventing unwanted complications. Next-generation sequencing (NGS) and detailed clinical and immunological evaluation can help early detect such disorders. This study aimed to confirm the diagnosis of two cases of autosomal recessive hyper-immunoglobulin E (IgE) syndrome (AR-HIES), presenting with irreversible eye involvement.
Two unrelated patients with suspected AR-HIES were referred to the Immunology, Asthma and Allergy Research Institute (IAARI), Tehran, Iran. Immunological screening tests were performed for AR-HIES, which showed elevated serum IgE levels, eosinophilia, and low T-lymphocyte responses. NGS was performed, and the results were confirmed by Sanger sequencing.
Sequence analysis showed a mutation in intron 17 of the dedicator of cytokinesis 8 (DOCK8) gene in the first patient, and a homozygous three base-pair deletion in exon 45 of DOCK8 in the second patient. This is the first time such mutations are reported and these variants are predicted to be damaging. Both patients suffered from persistent viral infections along with cytomegalovirus (CMV) retinitis.
Suspicion of these two novel DOCK8 mutations can benefit patients presenting with recalcitrant ophthalmic viral involvements and relevant immunological test results. This would lead to earlier referrals for immunologic and genetic confirmation and thus, a more timely intervention with hematopoietic stem cell transplantation (HSCT).

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Files	XML PDF (753KB)
Issue	Vol 21 No 3 (2022)
Section	Case Report(s)
DOI	https://doi.org/10.18502/ijaai.v21i3.9809
Keywords
Cytomegalovirus DOCK8 protein, human Hyperimmunoglobulin E syndrome Retinitis

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Saghafi S, Zandieh F, Fazlollahi MR, Glocker C, Frede N, Buchta M, Yang L, Mahmoudi AH, Houshmand M, Pourpak Z, Grimbacher B, Moin M. Confirmation of Hyperimmunoglobulin E Syndrome in Two Patients with an Ocular Problem: Detection of Two New DOCK8 Mutations. Iran J Allergy Asthma Immunol. 2022;21(3):355-363.

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