Mosaic RAS/MAPK variants cause sporadic vascular malformations which respond to targeted therapy.

ABSTRACT:

Background

Sporadic vascular malformations (VMs) are complex congenital anomalies of blood vessels that lead to stroke, life-threatening bleeds, disfigurement, overgrowth, and/or pain. Therapeutic options are severely limited, and multidisciplinary management remains challenging, particularly for high-flow arteriovenous malformations (AVM).

Methods

To investigate the pathogenesis of sporadic intracranial and extracranial VMs in 160 children in which known genetic causes had been excluded, we sequenced DNA from affected tissue and optimized analysis for detection of low mutant allele frequency.

Results

We discovered multiple mosaic-activating variants in 4 genes of the RAS/MAPK pathway, KRAS, NRAS, BRAF, and MAP2K1, a pathway commonly activated in cancer and responsibl

SUBMITTER: Al-Olabi L 

PROVIDER: S-EPMC5873857 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature