CASE REPORT article

Front. Cardiovasc. Med.

Sec. Cardiovascular Genetics and Systems Medicine

Volume 12 - 2025 | doi: 10.3389/fcvm.2025.1550523

Case Report: A heterozygous loss-of-function variant of the ERG gene in a family with vascular pathologies

Provisionally accepted
Philipp ErhartPhilipp Erhart1*Nicola DikowNicola Dikow2Eva M. C. SchwaiboldEva M. C. Schwaibold2Susanne DihlmannSusanne Dihlmann1Caspar Grond-GinsbachCaspar Grond-Ginsbach1Daniel KörferDaniel Körfer1Christian P. SchaafChristian P. Schaaf2Dittmar BöcklerDittmar Böckler1Jiarna R. ZerellaJiarna R. Zerella3Hamish S ScottHamish S Scott3Christopher Norman HahnChristopher Norman Hahn3Felix MarbachFelix Marbach4
  • 1Department of Vascular and Endovascular Surgery, Heidelberg University Hospital, Heidelberg, Baden-Württemberg, Germany
  • 2Institute of Human Genetics, University Hospital Heidelberg, Heidelberg, Baden-Württemberg, Germany
  • 3Molecular Pathology Research Laboratory, SA Pathology and University of South Australia, Adelaide, Australia
  • 4Institute of Human Genetics, University Hospital Bonn, Bonn, North Rhine-Westphalia, Germany

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The transcription factor ERG (erythroblast transformation-specific-related gene) has been identified as a key regulator of vascular function by suppressing inflammation in endothelial cells (ECs). Dysregulation of ERG due to genetic risk variants is linked to chronic inflammation in conditions such as atherosclerosis and aortic aneurysms.Case presentation: This research work investigates the role of the ERG gene in the development of a systemic arterial aneurysm manifestation. Given the previous implication of ERG in vascular development, we now report a loss-of-function variant (Leu212*) in the ERG gene, segregating in a family with vascular pathologies. Multiple arterial aneurysms were observed in one family member, and early onset of vascular-associated stroke in another individual carrying the familial ERG variant. Histological analysis of arterial aneurysm specimen showed comparable expression of ERG in endothelial cells of the vasa vasorum in samples from the patient and controls.Our report discusses the possibility that loss-of-function variants in ERG may act as a risk factor for arterial disease.

Keywords: Multiple arterial aneurysms, erg, Abdominal Aortic Aneurysm, loss-of-function variant, Haploinsufficiency

Received: 23 Dec 2024; Accepted: 07 May 2025.

Copyright: © 2025 Erhart, Dikow, Schwaibold, Dihlmann, Grond-Ginsbach, Körfer, Schaaf, Böckler, Zerella, Scott, Hahn and Marbach. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Philipp Erhart, Department of Vascular and Endovascular Surgery, Heidelberg University Hospital, Heidelberg, 69120, Baden-Württemberg, Germany

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