Elsevier

Gene Reports

Volume 29, December 2022, 101705
Gene Reports

Whole exome sequencing identifies a rare variant in MAS1 gene in a subject with lethal COVID-19

https://doi.org/10.1016/j.genrep.2022.101705Get rights and content
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Highlights

  • Genetic variants can contribute to cardiovascular complications in severe COVID-19.

  • WES in a family identified a variant in a new candidate gene for severe COVID-19.

  • Variants in MAS1 can alter the ACE2/Ang-(1–7)/Mas1 axis and cause severe COVID-19.

Abstract

COVID-19 may be considered a multifactorial disease caused by the interaction between the virus itself, as the environmental contribute, and the genetic background of the host. SARS-CoV-2 infection occurs through the interaction between the spike protein and ACE2, a receptor in the host cells. Clinically, COVID-19 is characterized by a high heterogeneity in symptomatology ranging from asymptomatic to severe symptoms, and even worsening to death. This variability relies on the host genomic profile and other individual comorbidities. We performed exome analysis in one family displaying a variable spectrum of SARS-CoV-2 infection despite a common exposure. After segregation analysis, we found that the c.446C>T p.(S149L) in MAS1 gene was exclusively present in the individual with severe COVID-19, who died because of pneumonia and multiple thrombotic events. MAS1 encodes a receptor for Ang1–7 in the renin-angiotensin system (RAS) with an anti-inflammatory, anti-fibrotic and anti-angiogenic effect. We hypothesize that downregulation of RAS, due to this rare variant, might impair the protective effect and concur to the clinical severity of the disease. Our results support the protective role of the ACE2/Ang-(1–7)/Mas1 axis and the potential danger of its dysregulation leading to severe COVID-19 disease; if further confirmed, these findings will be useful for management of critically ill patients.

Keywords

COVID-19
Whole exome sequencing
SARS-CoV-2
Renin-angiotensin system

Data availability

Data will be made available on request.

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