Carriers of single pathogenic variants of the CFTR (cystic fibrosis transmembrane conductance regulator) gene have a higher risk of severe COVID-19 and 14-day death. The machine learning post-Mendelian model pinpointed CFTR as a bidirectional modulator of COVID-19 outcomes. Here, we demonstrate that the rare complex allele [G576V;R668C] is associated with a milder disease via a gain-of-function mechanism. Conversely, CFTR ultra-rare alleles with reduced function are associated with disease severity either alone (dominant disorder) or with another hypomorphic allele in the second chromosome (recessive disorder) with a global residual CFTR activity between 50 to 91%. Furthermore, we characterized novel CFTR complex alleles, including [A238V;F508del], [R74W;D1270N;V201M], [I1027T;F508del], [I506V;D1168G], and simple alleles, including R347C, F1052V, Y625N, I328V, K68E, A309D, A252T, G542*, V562I, R1066H, I506V, I807M, which lead to a reduced CFTR function and thus, to more severe COVID-19. In conclusion, CFTR genetic analysis is an important tool in identifying patients at risk of severe COVID-19.

Gain- and Loss-of-Function CFTR Alleles Are Associated with COVID-19 Clinical Outcomes / Baldassarri, Margherita; Zguro, Kristina; Tomati, Valeria; Pastorino, Cristina; Fava, Francesca; Croci, Susanna; Bruttini, Mirella; Picchiotti, Nicola; Furini, Simone; Pedemonte, Nicoletta; Gabbi, Chiara; Renieri, Alessandra; Fallerini, Chiara. - In: CELLS. - ISSN 2073-4409. - ELETTRONICO. - 11:24(2022), pp. 4096.1-4096.20. [10.3390/cells11244096]

Gain- and Loss-of-Function CFTR Alleles Are Associated with COVID-19 Clinical Outcomes

Furini, Simone;
2022

Abstract

Carriers of single pathogenic variants of the CFTR (cystic fibrosis transmembrane conductance regulator) gene have a higher risk of severe COVID-19 and 14-day death. The machine learning post-Mendelian model pinpointed CFTR as a bidirectional modulator of COVID-19 outcomes. Here, we demonstrate that the rare complex allele [G576V;R668C] is associated with a milder disease via a gain-of-function mechanism. Conversely, CFTR ultra-rare alleles with reduced function are associated with disease severity either alone (dominant disorder) or with another hypomorphic allele in the second chromosome (recessive disorder) with a global residual CFTR activity between 50 to 91%. Furthermore, we characterized novel CFTR complex alleles, including [A238V;F508del], [R74W;D1270N;V201M], [I1027T;F508del], [I506V;D1168G], and simple alleles, including R347C, F1052V, Y625N, I328V, K68E, A309D, A252T, G542*, V562I, R1066H, I506V, I807M, which lead to a reduced CFTR function and thus, to more severe COVID-19. In conclusion, CFTR genetic analysis is an important tool in identifying patients at risk of severe COVID-19.
2022
Gain- and Loss-of-Function CFTR Alleles Are Associated with COVID-19 Clinical Outcomes / Baldassarri, Margherita; Zguro, Kristina; Tomati, Valeria; Pastorino, Cristina; Fava, Francesca; Croci, Susanna; Bruttini, Mirella; Picchiotti, Nicola; Furini, Simone; Pedemonte, Nicoletta; Gabbi, Chiara; Renieri, Alessandra; Fallerini, Chiara. - In: CELLS. - ISSN 2073-4409. - ELETTRONICO. - 11:24(2022), pp. 4096.1-4096.20. [10.3390/cells11244096]
Baldassarri, Margherita; Zguro, Kristina; Tomati, Valeria; Pastorino, Cristina; Fava, Francesca; Croci, Susanna; Bruttini, Mirella; Picchiotti, Nicola; Furini, Simone; Pedemonte, Nicoletta; Gabbi, Chiara; Renieri, Alessandra; Fallerini, Chiara
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/952699
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