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

Shiva Saghafi; Fariborz Zandieh; Mohammad Reza Fazlollahi; Cristina Glocker; Natalie Frede; Mary Buchta; Linlin Yang; Amir Hossein Mahmoudi; Massoud Houshmand; Zahra Pourpak; Bodo  Grimbacher; Mostafa Moin

doi:10.18502/ijaai.v21i3.9809

Shiva Saghafi Immunology, Asthma and Allergy Research Institute, Tehran University of Medical Sciences, Tehran, Iran
Fariborz Zandieh Department of Asthma, Allergy, and Immunology, Bahrami Children Hospital, Tehran University of Medical Sciences, Tehran, Iran
Mohammad Reza Fazlollahi Immunology, Asthma and Allergy Research Institute, Tehran University of Medical Sciences, Tehran, Iran
Cristina Glocker Institute for Immunodeficiency, Center for Chronic Immunodeficiency (CCI), Medical Center, Faculty of Medicine, Albert Ludwig University of Freiburg, Freiburg, Germany
Natalie Frede Institute for Immunodeficiency, Center for Chronic Immunodeficiency (CCI), Medical Center, Faculty of Medicine, Albert Ludwig University of Freiburg, Freiburg, Germany
Mary Buchta Institute for Immunodeficiency, Center for Chronic Immunodeficiency (CCI), Medical Center, Faculty of Medicine, Albert Ludwig University of Freiburg, Freiburg, Germany
Linlin Yang Institute for Immunodeficiency, Center for Chronic Immunodeficiency (CCI), Medical Center, Faculty of Medicine, Albert Ludwig University of Freiburg, Freiburg, Germany
Amir Hossein Mahmoudi Novin Didegan Eye Clinic, Tehran, Iran
Massoud Houshmand Department of Medical Genetics, National Institute for Genetic Engineering and Biotechnology, Tehran, Iran
Zahra Pourpak Immunology, Asthma and Allergy Research Institute, Tehran University of Medical Sciences, Tehran, Iran
Bodo Grimbacher Institute for Immunodeficiency, Center for Chronic Immunodeficiency (CCI), Medical Center, Faculty of Medicine, Albert Ludwig University of Freiburg, Freiburg, Germany
Mostafa Moin Immunology, Asthma and Allergy Research Institute, Tehran University of Medical Sciences, Tehran, Iran

DOI: https://doi.org/10.18502/ijaai.v21i3.9809

Keywords: Cytomegalovirus; Human DOCK8; Hyperimmunoglobulin E syndrome; Retinitis

Abstract

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).