Publication Date
3-28-2025
Journal
Journal of Clinical Immunology
DOI
10.1007/s10875-025-01877-z
PMID
40153067
PMCID
PMC11953147
PubMedCentral® Posted Date
3-28-2025
PubMedCentral® Full Text Version
Post-print
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.
Keywords
Female, Humans, Male, COVID-19, GATA2 Deficiency, GATA2 Transcription Factor, GTPase-Activating Proteins, Haploinsufficiency, Pedigree, SARS-CoV-2, Guanine Nucleotide Exchange Factors, DOCK2 deficiency, GATA2 haploinsufficiency, Inborn Errors of Immunity, Lymphocytic vasculopathy, Human papillomavirus, COVID-19
Published Open-Access
yes
Recommended Citation
Biglari, Sajjad; Youssefian, Leila; Tabatabaiefar, Mohammad Amin; et al., "DOCK2 Deficiency and GATA2 Haploinsufficiency Can Underlie Critical Coronavirus Disease 2019 (COVID-19) Pneumonia" (2025). Faculty and Staff Publications. 5173.
https://digitalcommons.library.tmc.edu/baylor_docs/5173
Included in
Clinical Epidemiology Commons, COVID-19 Commons, Genetic Phenomena Commons, Genetic Processes Commons, Genetic Structures Commons, Medical Genetics Commons, Medical Molecular Biology Commons, Medical Specialties Commons