tetano
Editor, Senior Moderator
NPJ Genom Med
. 2021 Jul 1;6(1):55.
doi: 10.1038/s41525-021-00220-w.
TBK1 and TNFRSF13B mutations and an autoinflammatory disease in a child with lethal COVID-19
Axel Schmidt[SUP] #[/SUP][SUP] 1 [/SUP], Sophia Peters[SUP] #[/SUP][SUP] 1 [/SUP], Alexej Knaus[SUP] #[/SUP][SUP] 2 [/SUP], Hemmen Sabir[SUP] 3 [/SUP], Frauke Hamsen[SUP] 4 [/SUP], Carlo Maj[SUP] 2 [/SUP], Julia Fazaal[SUP] 1 [/SUP], Sugirthan Sivalingam[SUP] 2 5 6 [/SUP], Oleksandr Savchenko[SUP] 7 [/SUP], Aakash Mantri[SUP] 2 [/SUP], Dirk Holzinger[SUP] 4 [/SUP], Ulrich Neudorf[SUP] 4 [/SUP], Andreas Müller[SUP] 3 [/SUP], Kerstin U Ludwig[SUP] 1 [/SUP], Peter M Krawitz[SUP] 2 [/SUP], Hartmut Engels[SUP] 1 [/SUP], Markus M Nöthen[SUP] 8 [/SUP], Soyhan Bagci[SUP] 3 [/SUP]
Affiliations
Abstract
Among children, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections are typically mild. Here, we describe the case of a 3.5-year-old girl with an unusually severe presentation of coronavirus disease (COVID-19). The child had an autoinflammatory disorder of unknown etiology, which had been treated using prednisolone and methotrexate, and her parents were half cousins of Turkish descent. After 5 days of nonspecific viral infection symptoms, tonic-clonic seizures occurred followed by acute cardiac insufficiency, multi-organ insufficiency, and ultimate death. Trio exome sequencing identified a homozygous splice-variant in the gene TBK1, and a homozygous missense variant in the gene TNFRSF13B. Heterozygous deleterious variants in the TBK1 gene have been associated with severe COVID-19, and the variant in the TNFRSF13B gene has been associated with common variable immunodeficiency (CVID). We suggest that the identified variants, the autoinflammatory disorder and its treatment, or a combination of these factors probably predisposed to lethal COVID-19 in the present case.
. 2021 Jul 1;6(1):55.
doi: 10.1038/s41525-021-00220-w.
TBK1 and TNFRSF13B mutations and an autoinflammatory disease in a child with lethal COVID-19
Axel Schmidt[SUP] #[/SUP][SUP] 1 [/SUP], Sophia Peters[SUP] #[/SUP][SUP] 1 [/SUP], Alexej Knaus[SUP] #[/SUP][SUP] 2 [/SUP], Hemmen Sabir[SUP] 3 [/SUP], Frauke Hamsen[SUP] 4 [/SUP], Carlo Maj[SUP] 2 [/SUP], Julia Fazaal[SUP] 1 [/SUP], Sugirthan Sivalingam[SUP] 2 5 6 [/SUP], Oleksandr Savchenko[SUP] 7 [/SUP], Aakash Mantri[SUP] 2 [/SUP], Dirk Holzinger[SUP] 4 [/SUP], Ulrich Neudorf[SUP] 4 [/SUP], Andreas Müller[SUP] 3 [/SUP], Kerstin U Ludwig[SUP] 1 [/SUP], Peter M Krawitz[SUP] 2 [/SUP], Hartmut Engels[SUP] 1 [/SUP], Markus M Nöthen[SUP] 8 [/SUP], Soyhan Bagci[SUP] 3 [/SUP]
Affiliations
- PMID: 34210994
- DOI: 10.1038/s41525-021-00220-w
Abstract
Among children, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections are typically mild. Here, we describe the case of a 3.5-year-old girl with an unusually severe presentation of coronavirus disease (COVID-19). The child had an autoinflammatory disorder of unknown etiology, which had been treated using prednisolone and methotrexate, and her parents were half cousins of Turkish descent. After 5 days of nonspecific viral infection symptoms, tonic-clonic seizures occurred followed by acute cardiac insufficiency, multi-organ insufficiency, and ultimate death. Trio exome sequencing identified a homozygous splice-variant in the gene TBK1, and a homozygous missense variant in the gene TNFRSF13B. Heterozygous deleterious variants in the TBK1 gene have been associated with severe COVID-19, and the variant in the TNFRSF13B gene has been associated with common variable immunodeficiency (CVID). We suggest that the identified variants, the autoinflammatory disorder and its treatment, or a combination of these factors probably predisposed to lethal COVID-19 in the present case.