Familial occurrence of brain arteriovenous malformation: a novel ACVRL1 mutation detected by whole exome sequencing.
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.
Department of Neurosurgery, Bahçeşehir University Medical School, İstanbul, Turkey.
Baran
B
Yılmaz
Department of Neurosurgery, Bahçeşehir University Medical School, İstanbul, Turkey.
Zafer Orkun
ZO
Toktaş
Department of Neurosurgery, Bahçeşehir University Medical School, İstanbul, Turkey.
Akın
A
Akakın
Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada.
Semra
S
Işık
Yale Center for Genome Analysis, Orange; and.
Kaya
K
Bilguvar
Department of Neurosurgery, Bahçeşehir University Medical School, İstanbul, Turkey.
Türker
T
Kılıç
Department of Neurosurgery, Yale School of Medicine, New Haven, Connecticut.
Murat
M
Günel
D030301:Activin Receptors, Type II / Q000235:genetics*; D000328:Adult; D005260:Female; D006801:Humans; D002538:Intracranial Arteriovenous Malformations / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D000073359:Exome Sequencing; D055815:Young Adult
C425364:ACVRL1 protein, human; D030301:Activin Receptors, Type II
ACVRL1; AVM = arteriovenous malformation; HHT = hereditary hemorrhagic telangiectasia; TGF-β = transforming growth factor–β; brain arteriovenous malformation; familial disease; vascular disorders; whole exome sequencing