Duran, D;
Zeng, X;
Jin, SC;
Choi, J;
Nelson-Williams, C;
Yatsula, B;
Gaillard, J;
... Kahle, KT; + view all
(2019)
Mutations in Chromatin Modifier and Ephrin Signaling Genes in Vein of Galen Malformation.
Neuron
, 101
10.1016/j.neuron.2018.11.041.
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Abstract
Normal vascular development includes the formation and specification of arteries, veins, and intervening capillaries. Vein of Galen malformations (VOGMs) are among the most common and severe neonatal brain arterio-venous malformations, shunting arterial blood into the brain's deep venous system through aberrant direct connections. Exome sequencing of 55 VOGM probands, including 52 parent-offspring trios, revealed enrichment of rare damaging de novo mutations in chromatin modifier genes that play essential roles in brain and vascular development. Other VOGM probands harbored rare inherited damaging mutations in Ephrin signaling genes, including a genome-wide significant mutation burden in EPHB4. Inherited mutations showed incomplete penetrance and variable expressivity, with mutation carriers often exhibiting cutaneous vascular abnormalities, suggesting a two-hit mechanism. The identified mutations collectively account for ∼30% of studied VOGM cases. These findings provide insight into disease biology and may have clinical implications for risk assessment.
| Type: | Article |
|---|---|
| Title: | Mutations in Chromatin Modifier and Ephrin Signaling Genes in Vein of Galen Malformation |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.neuron.2018.11.041 |
| Publisher version: | https://doi.org/10.1016/j.neuron.2018.11.041 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | EPHB4, Vein of Galen malformation, arterio-venous malformation, chromatin modifier, de novo mutations, ephrin signaling, pediatric neurosurgery, whole exome sequencing |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharma and Bio Chemistry |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10066012 |
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