npj Genomic Medicine (Jul 2021)

TBK1 and TNFRSF13B mutations and an autoinflammatory disease in a child with lethal COVID-19

  • Axel Schmidt,
  • Sophia Peters,
  • Alexej Knaus,
  • Hemmen Sabir,
  • Frauke Hamsen,
  • Carlo Maj,
  • Julia Fazaal,
  • Sugirthan Sivalingam,
  • Oleksandr Savchenko,
  • Aakash Mantri,
  • Dirk Holzinger,
  • Ulrich Neudorf,
  • Andreas Müller,
  • Kerstin U. Ludwig,
  • Peter M. Krawitz,
  • Hartmut Engels,
  • Markus M. Nöthen,
  • Soyhan Bagci

DOI
https://doi.org/10.1038/s41525-021-00220-w
Journal volume & issue
Vol. 6, no. 1
pp. 1 – 5

Abstract

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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.