Matrisome and Immune Pathways Contribute to Extreme Vascular Outcomes in Williams-Beuren Syndrome.

ABSTRACT:

Background

Supravalvar aortic stenosis (SVAS) is a characteristic feature of Williams-Beuren syndrome (WBS). Its severity varies: ~20% of people with Williams-Beuren syndrome have SVAS requiring surgical intervention, whereas ~35% have no appreciable SVAS. The remaining individuals have SVAS of intermediate severity. Little is known about genetic modifiers that contribute to this variability.

Methods and results

We performed genome sequencing on 473 individuals with Williams-Beuren syndrome and developed strategies for modifier discovery in this rare disease population. Approaches include extreme phenotyping and nonsynonymous variant prioritization, followed by gene set enrichment and pathway-level association tests. We next used GTEx v8 and proteomic data sets to verify exp

SUBMITTER: Liu D 

PROVIDER: S-EPMC11056152 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature