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Mutations in the ENG, ACVRL1, and SMAD4 genes and clinical manifestations of hereditary haemorrhagic telangiectasia: experience from the Center for Osler’s Disease, Uppsala University Hospital

Aim: The aim of this retrospective single-centre study was to evaluate whether mutations in the ENG, ACVRL1, and SMAD4 genes were associated with different phenotypes in hereditary haemorrhagic telangiectasia (HHT). Methods: The case records of 21 HHT patients with verified mutations in ENG, ACVRL1,...

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Autores principales: Karlsson, Torbjörn, Cherif, Honar
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6198721/
https://www.ncbi.nlm.nih.gov/pubmed/30251589
http://dx.doi.org/10.1080/03009734.2018.1483452
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author Karlsson, Torbjörn
Cherif, Honar
author_facet Karlsson, Torbjörn
Cherif, Honar
author_sort Karlsson, Torbjörn
collection PubMed
description Aim: The aim of this retrospective single-centre study was to evaluate whether mutations in the ENG, ACVRL1, and SMAD4 genes were associated with different phenotypes in hereditary haemorrhagic telangiectasia (HHT). Methods: The case records of 21 HHT patients with verified mutations in ENG, ACVRL1, or SMAD4 genes were reviewed. The numbers of HHT diagnostic criteria fulfilled for the three genotypes were compared, as was the prevalence of complications such as iron deficiency anaemia, gastrointestinal haemorrhage, stroke, and cerebral abscess. Results: Our results indicate that mutations in the ENG (HHT1), ACVRL1 (HHT2), and SMAD4 genes result in different HHT phenotypes. Epistaxis debuts earlier and may be more severe in HHT1 than in HHT2. The prevalence of pulmonary arteriovenous malformations (AVM) is higher in HHT type 1, whereas hepatic AVMs are more common in HHT2. One patient with mutations in both ENG and ACVRL1 genes was identified, as were two SMAD4-mutated patients suffering from the overlapping juvenile polyposis-HHT syndrome. Nearly one in five patients in our HHT population has been diagnosed with stroke or cerebral abscess, indicating a high prevalence of cerebral complications. Conclusion: Our results showing that ENG and ACVRL1 gene mutations result in different HHT phenotypes confirm the results from other HHT centres worldwide. Cerebral complications of HHT are common, underscoring the importance of regular screening for pulmonary AVMs and early intervention against such AVMs. We have identified an HHT patient with simultaneous mutations in the ENG and ACVRL1 genes. Surprisingly, this patient has had a mild course of the disease.
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spelling pubmed-61987212018-10-24 Mutations in the ENG, ACVRL1, and SMAD4 genes and clinical manifestations of hereditary haemorrhagic telangiectasia: experience from the Center for Osler’s Disease, Uppsala University Hospital Karlsson, Torbjörn Cherif, Honar Ups J Med Sci Article Aim: The aim of this retrospective single-centre study was to evaluate whether mutations in the ENG, ACVRL1, and SMAD4 genes were associated with different phenotypes in hereditary haemorrhagic telangiectasia (HHT). Methods: The case records of 21 HHT patients with verified mutations in ENG, ACVRL1, or SMAD4 genes were reviewed. The numbers of HHT diagnostic criteria fulfilled for the three genotypes were compared, as was the prevalence of complications such as iron deficiency anaemia, gastrointestinal haemorrhage, stroke, and cerebral abscess. Results: Our results indicate that mutations in the ENG (HHT1), ACVRL1 (HHT2), and SMAD4 genes result in different HHT phenotypes. Epistaxis debuts earlier and may be more severe in HHT1 than in HHT2. The prevalence of pulmonary arteriovenous malformations (AVM) is higher in HHT type 1, whereas hepatic AVMs are more common in HHT2. One patient with mutations in both ENG and ACVRL1 genes was identified, as were two SMAD4-mutated patients suffering from the overlapping juvenile polyposis-HHT syndrome. Nearly one in five patients in our HHT population has been diagnosed with stroke or cerebral abscess, indicating a high prevalence of cerebral complications. Conclusion: Our results showing that ENG and ACVRL1 gene mutations result in different HHT phenotypes confirm the results from other HHT centres worldwide. Cerebral complications of HHT are common, underscoring the importance of regular screening for pulmonary AVMs and early intervention against such AVMs. We have identified an HHT patient with simultaneous mutations in the ENG and ACVRL1 genes. Surprisingly, this patient has had a mild course of the disease. Taylor & Francis 2018-09 2018-09-25 /pmc/articles/PMC6198721/ /pubmed/30251589 http://dx.doi.org/10.1080/03009734.2018.1483452 Text en © 2018 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Article
Karlsson, Torbjörn
Cherif, Honar
Mutations in the ENG, ACVRL1, and SMAD4 genes and clinical manifestations of hereditary haemorrhagic telangiectasia: experience from the Center for Osler’s Disease, Uppsala University Hospital
title Mutations in the ENG, ACVRL1, and SMAD4 genes and clinical manifestations of hereditary haemorrhagic telangiectasia: experience from the Center for Osler’s Disease, Uppsala University Hospital
title_full Mutations in the ENG, ACVRL1, and SMAD4 genes and clinical manifestations of hereditary haemorrhagic telangiectasia: experience from the Center for Osler’s Disease, Uppsala University Hospital
title_fullStr Mutations in the ENG, ACVRL1, and SMAD4 genes and clinical manifestations of hereditary haemorrhagic telangiectasia: experience from the Center for Osler’s Disease, Uppsala University Hospital
title_full_unstemmed Mutations in the ENG, ACVRL1, and SMAD4 genes and clinical manifestations of hereditary haemorrhagic telangiectasia: experience from the Center for Osler’s Disease, Uppsala University Hospital
title_short Mutations in the ENG, ACVRL1, and SMAD4 genes and clinical manifestations of hereditary haemorrhagic telangiectasia: experience from the Center for Osler’s Disease, Uppsala University Hospital
title_sort mutations in the eng, acvrl1, and smad4 genes and clinical manifestations of hereditary haemorrhagic telangiectasia: experience from the center for osler’s disease, uppsala university hospital
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6198721/
https://www.ncbi.nlm.nih.gov/pubmed/30251589
http://dx.doi.org/10.1080/03009734.2018.1483452
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