학술논문
SARS-CoV-2 infection activating a novel variant of the NOTCH3 gene and subsequently causing development of CADASIL.
Document Type
Article
Author
Król, Zbigniew J.; Dorobek, Małgorzata; Dąbrowski, Maciej; Zielińska-Turek, Justyna; Mruk, Bartosz; Walecki, Jerzy; Sklinda, Katarzyna; Gil, Robert; Pawlak, Agnieszka; Wojtaszewska, Marzena; Lejman, Adrian; Dobosz, Paula; Zawadzki, Paweł; Pawłowska, Aneta; Szczepaniak, Michał; Król, Dorota; Zaczyński, Artur; Wierzba, Waldemar
Source
Subject
*GENETIC variation
*SARS-CoV-2
*WHOLE genome sequencing
*COVID-19
*GENETIC mutation
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Language
ISSN
1734-1922
Abstract
Introduction: In the following study we describe the diagnostic process and further case analysis of a 30-year-old woman admitted with typical COVID-19 symptoms, who subsequently developed additional symptoms suggesting cerebral autosomal dominant arteriopathy with sub-cortical infarcts and leukoencephalopathy (CADASIL). Material and methods: Other than the standard diagnostic procedures, whole genome sequencing (WGS) was used, which led to following findings. A new variant of the NOTCH3 gene, which led to CADASIL-like symptoms, was found, and it had been most likely activated by the SARS-CoV-2 infection. This novel variant in NOTCH3 has not been found in existing databases and has never been mentioned in research concerning CADASIL before. Results: Furthermore, after subjecting the patient's close relatives to WGS it was found that no other examined person demonstrated the same genetic mutation. Conclusions: It seems therefore that the new variant of NOTCH3 is of de novo origin in the patient's genome. Additionally, the relatively early onset of CADASIL and the unexpectedly severe COVID-19 infection suggest that the two occurred simultaneously: the infection with SARS-CoV-2 accelerated development of CADASIL symptoms and the unusual variant of the NOTCH3 gene contributed to the more severe course of COVID-19. [ABSTRACT FROM AUTHOR]