NOTCH3 variant position is associated with NOTCH3 aggregation load in CADASIL vasculature.

ABSTRACT:

Aims

CADASIL, the most prevalent hereditary cerebral small vessel disease, is caused by cysteine-altering NOTCH3 variants (NOTCH3^cys ) leading to vascular NOTCH3 protein aggregation. It has recently been shown that variants located in one of NOTCH3 protein epidermal growth-factor like repeat (EGFr) domains 1-6, are associated with a more severe phenotype than variants located in one of the EGFr domains 7-34. The underlying mechanism for this genotype-phenotype correlation is unknown. The aim of this study was to analyse whether NOTCH3^cys variant position is associated with NOTCH3 protein aggregation load.

Methods

We quantified vascular NOTCH3 aggregation in skin biopsies (n = 25) and brain tissue (n = 7) of CADASIL patients with a NOTCH3^cys E

SUBMITTER: Gravesteijn G 

PROVIDER: S-EPMC9291091 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature