RT Journal Article
SR Electronic
T1 Exome sequencing of 112 trios identifies recessive genetic variants in brain arteriovenous malformations
JF Journal of NeuroInterventional Surgery
JO J NeuroIntervent Surg
FD BMJ Publishing Group Ltd.
SP 568
OP 573
DO 10.1136/neurintsurg-2020-016469
VO 13
IS 6
A1 Mingqi Zhang
A1 Xinghuan Ding
A1 Qianqian Zhang
A1 Jian Liu
A1 Yisen Zhang
A1 Ying Zhang
A1 Zhongbin Tian
A1 Wenqiang Li
A1 Wei Zhu
A1 Huibin Kang
A1 Zhongxiao Wang
A1 Xinzhi Wu
A1 Chao Wang
A1 Xinjian Yang
A1 Kun Wang
YR 2021
UL http://jnis.bmj.com/content/13/6/568.abstract
AB Background Brain arteriovenous malformation (BAVM) is a main cause of cerebral hemorrhage and hemorrhagic stroke in adolescents. Morphologically, a BAVM is an abnormal connection between cerebrovascular arteries and veins. The genetic etiology of BAVMs has not been fully elucidated. In this study, we aim to investigate potential recessive genetic variants in BAVMs by interrogation of rare compound heterozygous variants.Methods We performed whole exome sequencing (WES) on 112 BAVM trios and analyzed the data for rare and deleterious compound heterozygous mutations associated with the disease.Results We identified 16 genes with compound heterozygous variants that were recurrent in more than one trio. Two genes (LRP2, MUC5B) were recurrently mutated in three trios. LRP2 has been previously associated with BAVM pathogenesis. Fourteen genes (MYLK, HSPG2, PEAK1, PIEZO1, PRUNE2, DNAH14, DNAH5, FCGBP, HERC2, HMCN1, MYH1, NHSL1, PLEC, RP1L1) were recurrently mutated in two trios, and five of these genes (MYLK, HSPG2, PEAK1, PIEZO1, PRUNE2) have been reported to play a role in angiogenesis or vascular diseases. Additionally, abnormal expression of the MYLK protein is related to spinal arteriovenous malformations.Conclusion Our study indicates that rare recessive compound heterozygous variants may underlie cases of BAVM. These findings improve our understanding of BAVM pathology and indicate genes for functional validation.Data are available upon reasonable request.