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

BackgroundThe 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 condit...

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Main Authors: Philipp Erhart, Nicola Dikow, Eva M. C. Schwaibold, Susanne Dihlmann, Caspar Grond-Ginsbach, Daniel Körfer, Christian P. Schaaf, Sabrina Oeser, Katrin Hinderhofer, Dittmar Böckler, Jiarna R. Zerella, Hamish S. Scott, Christopher N. Hahn, Felix Marbach
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-06-01
Series:Frontiers in Cardiovascular Medicine
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Online Access:https://www.frontiersin.org/articles/10.3389/fcvm.2025.1550523/full
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author Philipp Erhart
Nicola Dikow
Eva M. C. Schwaibold
Susanne Dihlmann
Caspar Grond-Ginsbach
Daniel Körfer
Christian P. Schaaf
Sabrina Oeser
Katrin Hinderhofer
Dittmar Böckler
Jiarna R. Zerella
Jiarna R. Zerella
Hamish S. Scott
Hamish S. Scott
Christopher N. Hahn
Christopher N. Hahn
Felix Marbach
Felix Marbach
author_facet Philipp Erhart
Nicola Dikow
Eva M. C. Schwaibold
Susanne Dihlmann
Caspar Grond-Ginsbach
Daniel Körfer
Christian P. Schaaf
Sabrina Oeser
Katrin Hinderhofer
Dittmar Böckler
Jiarna R. Zerella
Jiarna R. Zerella
Hamish S. Scott
Hamish S. Scott
Christopher N. Hahn
Christopher N. Hahn
Felix Marbach
Felix Marbach
author_sort Philipp Erhart
collection DOAJ
description BackgroundThe 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 presentationThis 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.ConclusionOur report discusses the possibility that loss-of-function variants in ERG may act as a risk factor for arterial disease.
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publishDate 2025-06-01
publisher Frontiers Media S.A.
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series Frontiers in Cardiovascular Medicine
spelling doaj-art-caf4f83de5f3420aa8b8076ba4e5d1932025-08-20T03:30:14ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2025-06-011210.3389/fcvm.2025.15505231550523Case Report: A heterozygous loss-of-function variant of the ERG gene in a family with vascular pathologiesPhilipp Erhart0Nicola Dikow1Eva M. C. Schwaibold2Susanne Dihlmann3Caspar Grond-Ginsbach4Daniel Körfer5Christian P. Schaaf6Sabrina Oeser7Katrin Hinderhofer8Dittmar Böckler9Jiarna R. Zerella10Jiarna R. Zerella11Hamish S. Scott12Hamish S. Scott13Christopher N. Hahn14Christopher N. Hahn15Felix Marbach16Felix Marbach17Department of Vascular and Endovascular Surgery, University Hospital Heidelberg, Heidelberg, GermanyInstitute of Human Genetics, Heidelberg University, Heidelberg, GermanyInstitute of Human Genetics, Heidelberg University, Heidelberg, GermanyDepartment of Vascular and Endovascular Surgery, University Hospital Heidelberg, Heidelberg, GermanyDepartment of Vascular and Endovascular Surgery, University Hospital Heidelberg, Heidelberg, GermanyDepartment of Vascular and Endovascular Surgery, University Hospital Heidelberg, Heidelberg, GermanyInstitute of Human Genetics, Heidelberg University, Heidelberg, GermanyInstitute of Human Genetics, Heidelberg University, Heidelberg, GermanyInstitute of Human Genetics, Heidelberg University, Heidelberg, GermanyDepartment of Vascular and Endovascular Surgery, University Hospital Heidelberg, Heidelberg, GermanyMolecular Pathology Research Laboratory, Centre for Cancer Biology, SA Pathology and University of South Australia, Adelaide, SA, AustraliaAdelaide Medical School, University of Adelaide, Adelaide, SA, AustraliaMolecular Pathology Research Laboratory, Centre for Cancer Biology, SA Pathology and University of South Australia, Adelaide, SA, AustraliaAdelaide Medical School, University of Adelaide, Adelaide, SA, AustraliaMolecular Pathology Research Laboratory, Centre for Cancer Biology, SA Pathology and University of South Australia, Adelaide, SA, AustraliaAdelaide Medical School, University of Adelaide, Adelaide, SA, AustraliaInstitute of Human Genetics, Heidelberg University, Heidelberg, GermanyInstitute of Human Genetics, Medical Faculty, University of Bonn, Bonn, GermanyBackgroundThe 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 presentationThis 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.ConclusionOur report discusses the possibility that loss-of-function variants in ERG may act as a risk factor for arterial disease.https://www.frontiersin.org/articles/10.3389/fcvm.2025.1550523/fullmultiple arterial aneurysmsERGabdominal aortic aneurysmloss-of-function varianthaploinsufficiency
spellingShingle Philipp Erhart
Nicola Dikow
Eva M. C. Schwaibold
Susanne Dihlmann
Caspar Grond-Ginsbach
Daniel Körfer
Christian P. Schaaf
Sabrina Oeser
Katrin Hinderhofer
Dittmar Böckler
Jiarna R. Zerella
Jiarna R. Zerella
Hamish S. Scott
Hamish S. Scott
Christopher N. Hahn
Christopher N. Hahn
Felix Marbach
Felix Marbach
Case Report: A heterozygous loss-of-function variant of the ERG gene in a family with vascular pathologies
Frontiers in Cardiovascular Medicine
multiple arterial aneurysms
ERG
abdominal aortic aneurysm
loss-of-function variant
haploinsufficiency
title Case Report: A heterozygous loss-of-function variant of the ERG gene in a family with vascular pathologies
title_full Case Report: A heterozygous loss-of-function variant of the ERG gene in a family with vascular pathologies
title_fullStr Case Report: A heterozygous loss-of-function variant of the ERG gene in a family with vascular pathologies
title_full_unstemmed Case Report: A heterozygous loss-of-function variant of the ERG gene in a family with vascular pathologies
title_short Case Report: A heterozygous loss-of-function variant of the ERG gene in a family with vascular pathologies
title_sort case report a heterozygous loss of function variant of the erg gene in a family with vascular pathologies
topic multiple arterial aneurysms
ERG
abdominal aortic aneurysm
loss-of-function variant
haploinsufficiency
url https://www.frontiersin.org/articles/10.3389/fcvm.2025.1550523/full
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