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J Neurosurg. 2017 Jun;126(6):1879-1883. doi: 10.3171/2016.6.JNS16665. Epub 2016 Sep 9.

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

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Department of Neurosurgery, Bahçeşehir University Medical School, İstanbul, Turkey.
Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada.
Yale Center for Genome Analysis, Orange; and.
Department of Neurosurgery, Yale School of Medicine, New Haven, Connecticut.


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. CONCLUSIONS Study results suggested that whole exome sequencing analysis is particularly useful in cases of locus heterogeneity and uncertain diagnostic classification schemes in patients with hereditary brain AVM.


ACVRL1; AVM = arteriovenous malformation; HHT = hereditary hemorrhagic telangiectasia; TGF-β = transforming growth factor–β; brain arteriovenous malformation; familial disease; vascular disorders; whole exome sequencing


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