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Distribution of Cerebrovascular Phenotypes According to Variants of the ENG and ACVRL1 Genes in Subjects with Hereditary Hemorrhagic Telangiectasia

Hereditary Hemorrhagic Telangiectasia (HHT) is an autosomal dominant disorder caused, in more than 80% of cases, by mutations of either the endoglin (ENG) or the activin A receptor-like type 1 (ACVRL1) gene. Several hundred variants have been identified in these HHT-causing genes, including deletion...

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Autores principales: Gaetani, Eleonora, Peppucci, Elisabetta, Agostini, Fabiana, Di Martino, Luigi, Lucci Cordisco, Emanuela, Sturiale, Carmelo L., Puca, Alfredo, Porfidia, Angelo, Alexandre, Andrea, Pedicelli, Alessandro, Pola, Roberto
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9146077/
https://www.ncbi.nlm.nih.gov/pubmed/35628811
http://dx.doi.org/10.3390/jcm11102685
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author Gaetani, Eleonora
Peppucci, Elisabetta
Agostini, Fabiana
Di Martino, Luigi
Lucci Cordisco, Emanuela
Sturiale, Carmelo L.
Puca, Alfredo
Porfidia, Angelo
Alexandre, Andrea
Pedicelli, Alessandro
Pola, Roberto
author_facet Gaetani, Eleonora
Peppucci, Elisabetta
Agostini, Fabiana
Di Martino, Luigi
Lucci Cordisco, Emanuela
Sturiale, Carmelo L.
Puca, Alfredo
Porfidia, Angelo
Alexandre, Andrea
Pedicelli, Alessandro
Pola, Roberto
author_sort Gaetani, Eleonora
collection PubMed
description Hereditary Hemorrhagic Telangiectasia (HHT) is an autosomal dominant disorder caused, in more than 80% of cases, by mutations of either the endoglin (ENG) or the activin A receptor-like type 1 (ACVRL1) gene. Several hundred variants have been identified in these HHT-causing genes, including deletions, missense and nonsense mutations, splice defects, duplications, and insertions. In this study, we have analyzed retrospectively collected images of magnetic resonance angiographies (MRA) of the brain of HHT patients, followed at the HHT Center of our University Hospital, and looked for the distribution of cerebrovascular phenotypes according to specific gene variants. We found that cerebrovascular malformations were heterogeneous among HHT patients, with phenotypes that ranged from classical arteriovenous malformations (AVM) to intracranial aneurysms (IA), developmental venous anomalies (DVA), and cavernous angiomas (CA). There was also wide heterogeneity among the variants of the ENG and ACVRL1 genes, which included known pathogenic variants, variants of unknown significance, variants pending classification, and variants which had not been previously reported. The percentage of patients with cerebrovascular malformations was significantly higher among subjects with ENG variants than ACVRL1 variants (25.0% vs. 13.1%, p < 0.05). The prevalence of neurovascular anomalies was different among subjects with different gene variants, with an incidence that ranged from 3.3% among subjects with the c.1231C > T, c.200G > A, or c.1120C > T missense mutations of the ACVRL1 gene, to 75.0% among subjects with the c.1435C > T missense mutation of the ACVRL1 gene. Further studies and larger sample sizes are required to confirm these findings.
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spelling pubmed-91460772022-05-29 Distribution of Cerebrovascular Phenotypes According to Variants of the ENG and ACVRL1 Genes in Subjects with Hereditary Hemorrhagic Telangiectasia Gaetani, Eleonora Peppucci, Elisabetta Agostini, Fabiana Di Martino, Luigi Lucci Cordisco, Emanuela Sturiale, Carmelo L. Puca, Alfredo Porfidia, Angelo Alexandre, Andrea Pedicelli, Alessandro Pola, Roberto J Clin Med Article Hereditary Hemorrhagic Telangiectasia (HHT) is an autosomal dominant disorder caused, in more than 80% of cases, by mutations of either the endoglin (ENG) or the activin A receptor-like type 1 (ACVRL1) gene. Several hundred variants have been identified in these HHT-causing genes, including deletions, missense and nonsense mutations, splice defects, duplications, and insertions. In this study, we have analyzed retrospectively collected images of magnetic resonance angiographies (MRA) of the brain of HHT patients, followed at the HHT Center of our University Hospital, and looked for the distribution of cerebrovascular phenotypes according to specific gene variants. We found that cerebrovascular malformations were heterogeneous among HHT patients, with phenotypes that ranged from classical arteriovenous malformations (AVM) to intracranial aneurysms (IA), developmental venous anomalies (DVA), and cavernous angiomas (CA). There was also wide heterogeneity among the variants of the ENG and ACVRL1 genes, which included known pathogenic variants, variants of unknown significance, variants pending classification, and variants which had not been previously reported. The percentage of patients with cerebrovascular malformations was significantly higher among subjects with ENG variants than ACVRL1 variants (25.0% vs. 13.1%, p < 0.05). The prevalence of neurovascular anomalies was different among subjects with different gene variants, with an incidence that ranged from 3.3% among subjects with the c.1231C > T, c.200G > A, or c.1120C > T missense mutations of the ACVRL1 gene, to 75.0% among subjects with the c.1435C > T missense mutation of the ACVRL1 gene. Further studies and larger sample sizes are required to confirm these findings. MDPI 2022-05-10 /pmc/articles/PMC9146077/ /pubmed/35628811 http://dx.doi.org/10.3390/jcm11102685 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Gaetani, Eleonora
Peppucci, Elisabetta
Agostini, Fabiana
Di Martino, Luigi
Lucci Cordisco, Emanuela
Sturiale, Carmelo L.
Puca, Alfredo
Porfidia, Angelo
Alexandre, Andrea
Pedicelli, Alessandro
Pola, Roberto
Distribution of Cerebrovascular Phenotypes According to Variants of the ENG and ACVRL1 Genes in Subjects with Hereditary Hemorrhagic Telangiectasia
title Distribution of Cerebrovascular Phenotypes According to Variants of the ENG and ACVRL1 Genes in Subjects with Hereditary Hemorrhagic Telangiectasia
title_full Distribution of Cerebrovascular Phenotypes According to Variants of the ENG and ACVRL1 Genes in Subjects with Hereditary Hemorrhagic Telangiectasia
title_fullStr Distribution of Cerebrovascular Phenotypes According to Variants of the ENG and ACVRL1 Genes in Subjects with Hereditary Hemorrhagic Telangiectasia
title_full_unstemmed Distribution of Cerebrovascular Phenotypes According to Variants of the ENG and ACVRL1 Genes in Subjects with Hereditary Hemorrhagic Telangiectasia
title_short Distribution of Cerebrovascular Phenotypes According to Variants of the ENG and ACVRL1 Genes in Subjects with Hereditary Hemorrhagic Telangiectasia
title_sort distribution of cerebrovascular phenotypes according to variants of the eng and acvrl1 genes in subjects with hereditary hemorrhagic telangiectasia
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9146077/
https://www.ncbi.nlm.nih.gov/pubmed/35628811
http://dx.doi.org/10.3390/jcm11102685
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