tetano
Editor, Senior Moderator
J Clin Immunol
. 2025 Mar 28;45(1):85.
doi: 10.1007/s10875-025-01877-z. DOCK2 Deficiency and GATA2 Haploinsufficiency Can Underlie Critical Coronavirus Disease 2019 (COVID-19) Pneumonia
Sajjad Biglari[SUP] #[/SUP][SUP] 1 [/SUP], Leila Youssefian[SUP] #[/SUP][SUP] 2 [/SUP], Mohammad Amin Tabatabaiefar[SUP] 1 [/SUP], Amir Hossein Saeidian[SUP] 3 4 [/SUP], Bahareh Abtahi-Naeini[SUP] 5 6 [/SUP], Erfan Khorram[SUP] 7 [/SUP], Roya Sherkat[SUP] 8 [/SUP], Atefeh Sohanforooshan Moghaddam[SUP] 9 [/SUP], Fatemeh Mohaghegh[SUP] 10 [/SUP], Maziyar Rahimi[SUP] 11 [/SUP], Hamid Rahimi[SUP] 12 [/SUP], Sharareh Babaei[SUP] 13 [/SUP], Mohammad Shahrooei[SUP] 14 15 [/SUP], Nikoo Mozafari[SUP] 16 [/SUP], Shirin Zaresharifi[SUP] 16 [/SUP], Fatemeh Vahidnezhad[SUP] 17 [/SUP], Vida Homayouni[SUP] 8 [/SUP], Lam C Tsoi[SUP] 18 [/SUP], Johann E Gudjonsson[SUP] 18 [/SUP], Hakon Hakonarson[SUP] 3 19 20 [/SUP], Jean-Laurent Casanova[SUP] 21 22 23 24 25 [/SUP], Emmanuelle Jouanguy[SUP] 21 22 23 [/SUP], Vivien Béziat[SUP] 21 22 23 [/SUP], Qian Zhang[SUP] 21 22 23 [/SUP], Aurélie Cobat[SUP] 21 22 23 [/SUP], Hassan Vahidnezhad[SUP] 26 27 28 29 [/SUP]
Affiliations
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: COVID-19; DOCK2 deficiency; GATA2 haploinsufficiency; Human papillomavirus; Inborn Errors of Immunity; Lymphocytic vasculopathy.
. 2025 Mar 28;45(1):85.
doi: 10.1007/s10875-025-01877-z. DOCK2 Deficiency and GATA2 Haploinsufficiency Can Underlie Critical Coronavirus Disease 2019 (COVID-19) Pneumonia
Sajjad Biglari[SUP] #[/SUP][SUP] 1 [/SUP], Leila Youssefian[SUP] #[/SUP][SUP] 2 [/SUP], Mohammad Amin Tabatabaiefar[SUP] 1 [/SUP], Amir Hossein Saeidian[SUP] 3 4 [/SUP], Bahareh Abtahi-Naeini[SUP] 5 6 [/SUP], Erfan Khorram[SUP] 7 [/SUP], Roya Sherkat[SUP] 8 [/SUP], Atefeh Sohanforooshan Moghaddam[SUP] 9 [/SUP], Fatemeh Mohaghegh[SUP] 10 [/SUP], Maziyar Rahimi[SUP] 11 [/SUP], Hamid Rahimi[SUP] 12 [/SUP], Sharareh Babaei[SUP] 13 [/SUP], Mohammad Shahrooei[SUP] 14 15 [/SUP], Nikoo Mozafari[SUP] 16 [/SUP], Shirin Zaresharifi[SUP] 16 [/SUP], Fatemeh Vahidnezhad[SUP] 17 [/SUP], Vida Homayouni[SUP] 8 [/SUP], Lam C Tsoi[SUP] 18 [/SUP], Johann E Gudjonsson[SUP] 18 [/SUP], Hakon Hakonarson[SUP] 3 19 20 [/SUP], Jean-Laurent Casanova[SUP] 21 22 23 24 25 [/SUP], Emmanuelle Jouanguy[SUP] 21 22 23 [/SUP], Vivien Béziat[SUP] 21 22 23 [/SUP], Qian Zhang[SUP] 21 22 23 [/SUP], Aurélie Cobat[SUP] 21 22 23 [/SUP], Hassan Vahidnezhad[SUP] 26 27 28 29 [/SUP]
Affiliations
- PMID: 40153067
- PMCID: PMC11953147
- DOI: 10.1007/s10875-025-01877-z
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: COVID-19; DOCK2 deficiency; GATA2 haploinsufficiency; Human papillomavirus; Inborn Errors of Immunity; Lymphocytic vasculopathy.