Familial occurrence of brain arteriovenous malformation: A novel ACVRL1 mutation detected by whole exome sequencing

Abstract

OBJECTIVE Brain arteriovenous malformations (AVMs) can occur in patients with hereditary hemorrhagic telangiectasia (HHT). However, brain AVM without HHT has also been reported. Using whole exome sequencing, the authors performed comprehensive genomic characterization of a 6-person Turkish family with 3 cases of brain AVM without HHT. METHODS Three siblings with brain AVM, one of whom also had spinal AVM, were evaluated. The parents and the fourth sibling had no AVM on cranial MRI. The authors performed a whole exome capture and Illumina sequencing on blood samples from 2 siblings with AVM. RESULTS An ACVRL1 heterozygous mutation (p.Lys332Glu) was identified in 2 patients via whole exome sequencing. Variant segregation was confirmed using direct Sanger sequencing.