DOCK2 Deficiency and GATA2 Haploinsufficiency Can Underlie Critical Coronavirus Disease 2019 (COVID-19) Pneumonia

The life-threatening coronavirus disease 2019 (COVID-19) affects about 1 in 1,000 healthy people under 50 without underlying conditions. Among patients with critical COVID-19 pneumonia, rare germline variants at genes controlling type I IFN immunity have been reported in up to 5% of patients. Causal etiologies in 80-85% of cases are still unknown. We analyzed two families with hypoxemic COVID-19 pneumonia for known single-gene inborn errors of immunity. In Family 1, two siblings with critical COVID-19 were homozygous for a DOCK2 variant, c.3624+5G>A. DOCK2 deficiency is a known T-cell disorder underlying severe viral diseases. The variant resulted in skipping exon 35, which was predicted to produce a frameshift truncated protein (p.L1157Ifs*12). The proband showed markedly decreased blood CD4 T-helper cell counts, impaired T lymphocyte transformation test, and increased serum IgG, IgA, and IgE levels, as documented in other DOCK2-deficient patients. In Family 2, the proband had lethal COVID-19 and HPV-2-associated multiple recalcitrant warts. She was heterozygous for a deletion in GATA2:c.1075_1102del28, p.W360Sfs*18. GATA2 haploinsufficiency is a known cause of severe viral diseases due to a lack of plasmacytoid dendritic cell (pDC) development. The proband had monocytopenia and a lack of circulating pDCs, as reported in other patients with GATA2 haploinsufficiency. Overall, both DOCK2 deficiency and GATA2 haploinsufficiency are associated with critical and often fatal COVID-19 pneumonia.

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Publication Details

Journal
Journal of Clinical Immunology
Published
2025-03-28
DOI
https://doi.org/10.1007/s10875-025-01877-z
Citations
2
Primary Topic
Immunodeficiency and Autoimmune Disorders
Type
article
Field-Weighted Citation Impact
1.59

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article

DOCK2 Deficiency and GATA2 Haploinsufficiency Can Underlie Critical Coronavirus Disease 2019 (COVID-19) Pneumonia

Vida Homayouni, Amir Hossein Saeidian, Mojtaba A Rahimi, Mohammad Amin Tabatabaiefar et al.
2 citations
Journal of Clinical Immunology
Immunodeficiency and Autoimmune Disorders
1.59
article

DOCK2 Deficiency and GATA2 Haploinsufficiency Can Underlie Critical Coronavirus Disease 2019 (COVID-19) Pneumonia

Vida Homayouni, Amir Hossein Saeidian, Mojtaba A Rahimi, Mohammad Amin Tabatabaiefar, Erfan Khorram, Bahareh Abtahi‐Naeini, Nikoo Mozafari, Sharareh Babaei, Fatemeh Vahidnezhad, Lam C. Tsoi, Johann Eli Gudjonsson, Emmanuelle Jouanguy, Hassan Vahidnezhad, Shirin Zaresharifi, Vivien Béziat, Mohammad Shahrooei, Leila Youssefian, Håkon Håkonarson, Fatemeh Mohaghegh, Atefeh Sohanforooshan Moghaddam, Hamid Rahimi, Sajjad Biglari, Qian Zhang, Jean-Laurent Casanova, Aurélie Cobat, Roya Sherkat
article en
2 citations

Abstract

The life-threatening coronavirus disease 2019 (COVID-19) affects about 1 in 1,000 healthy people under 50 without underlying conditions. Among patients with critical COVID-19 pneumonia, rare germline variants at genes controlling type I IFN immunity have been reported in up to 5% of patients. Causal etiologies in 80-85% of cases are still unknown. We analyzed two families with hypoxemic COVID-19 pneumonia for known single-gene inborn errors of immunity. In Family 1, two siblings with critical COVID-19 were homozygous for a DOCK2 variant, c.3624+5G>A. DOCK2 deficiency is a known T-cell disorder underlying severe viral diseases. The variant resulted in skipping exon 35, which was predicted to produce a frameshift truncated protein (p.L1157Ifs*12). The proband showed markedly decreased blood CD4 T-helper cell counts, impaired T lymphocyte transformation test, and increased serum IgG, IgA, and IgE levels, as documented in other DOCK2-deficient patients. In Family 2, the proband had lethal COVID-19 and HPV-2-associated multiple recalcitrant warts. She was heterozygous for a deletion in GATA2:c.1075_1102del28, p.W360Sfs*18. GATA2 haploinsufficiency is a known cause of severe viral diseases due to a lack of plasmacytoid dendritic cell (pDC) development. The proband had monocytopenia and a lack of circulating pDCs, as reported in other patients with GATA2 haploinsufficiency. Overall, both DOCK2 deficiency and GATA2 haploinsufficiency are associated with critical and often fatal COVID-19 pneumonia.

Journal of Clinical ImmunologyVol. 45(1)
Isfahan University of Medical Sciences (IR), Shahed University (IR), City Of Hope National Medical Center (US), Howard Hughes Medical Institute (US), Inserm (FR), University of Shahrood (IR), Baylor College of Medicine (US), Islamic Azad University North Tehran Branch (IR), Université Paris Cité (FR), University of Maryland Eastern Shore (US), University of Michigan (US), Hospital for Sick Children Pediatric Center (US), Institut des Maladies Génétiques Imagine (FR), Shahid Beheshti University of Medical Sciences (IR), University of Pennsylvania (US), Rockefeller University (US), UCLouvain (BE)
LEO Fondet, National Institutes of Health
Good health and well-being
Openalex Percentile: Top 18%
Immunodeficiency and Autoimmune Disorders
1.59
DOIOpen Access PDFOpenAlex
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