Heterozygous NOTCH1 Variants Cause CNS Immune Activation and Microangiopathy.
Journal
Annals of neurology
ISSN: 1531-8249
Titre abrégé: Ann Neurol
Pays: United States
ID NLM: 7707449
Informations de publication
Date de publication:
11 2022
11 2022
Historique:
revised:
06
08
2022
received:
26
02
2022
accepted:
09
08
2022
pubmed:
11
8
2022
medline:
26
10
2022
entrez:
10
8
2022
Statut:
ppublish
Résumé
NOTCH1 belongs to the NOTCH family of proteins that regulate cell fate and inflammatory responses. Somatic and germline NOTCH1 variants have been implicated in cancer, Adams-Oliver syndrome, and cardiovascular defects. We describe 7 unrelated patients grouped by the presence of leukoencephalopathy with calcifications and heterozygous de novo gain-of-function variants in NOTCH1. Immunologic profiling showed upregulated CSF IP-10, a cytokine secreted downstream of NOTCH1 signaling. Autopsy revealed extensive leukoencephalopathy and microangiopathy with vascular calcifications. This evidence implicates that heterozygous gain-of-function variants in NOTCH1 lead to a chronic central nervous system (CNS) inflammatory response resulting in a calcifying microangiopathy with leukoencephalopathy. ANN NEUROL 2022;92:895-901.
Substances chimiques
Receptor, Notch1
0
Chemokine CXCL10
0
NOTCH1 protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
895-901Commentaires et corrections
Type : CommentIn
Type : CommentIn
Informations de copyright
© 2022 American Neurological Association.
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