INFECTIOUS DISEASES / CLINICAL RESEARCH
SARS-CoV-2 infection activating a novel variant of the NOTCH3 gene and subsequently causing development of CADASIL
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1
Central Clinical Hospital of the Ministry of Interior and Administration, Warsaw, Poland
3
Department of Radiology, Centre of Postgraduate Medical Education, Warsaw, Poland
Submission date: 2021-09-30
Final revision date: 2022-01-19
Acceptance date: 2022-02-27
Online publication date: 2022-04-04
Publication date: 2023-11-13
Corresponding author
Waldemar Wierzba
Central Clinical,
Hospital of the
Ministry of Interior
and Administration,
Warsaw, Poland
Arch Med Sci 2023;19(6):1781–1794
KEYWORDS
TOPICS
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.