A population-based survey of FBN1 variants in Iceland reveals underdiagnosis of Marfan syndrome
Publisher Copyright: © 2023, The Author(s). Marfan syndrome (MFS) is an autosomal dominant condition characterized by aortic aneurysm, skeletal abnormalities, and lens dislocation, and is caused by variants in the FBN1 gene. To explore causes of MFS and the prevalence of the disease in Iceland we co...
Published in: | European Journal of Human Genetics |
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Online Access: | https://hdl.handle.net/20.500.11815/4508 https://doi.org/10.1038/s41431-023-01455-0 |
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ftopinvisindi:oai:opinvisindi.is:20.500.11815/4508 2023-11-12T04:18:59+01:00 A population-based survey of FBN1 variants in Iceland reveals underdiagnosis of Marfan syndrome Klemenzdottir, Elin Ola Arnadottir, Gudny A Jensson, Brynjar Orn Jonasdottir, Adalbjorg Katrinardottir, Hildigunnur Fridriksdottir, Run Jonasdottir, Aslaug Sigurdsson, Asgeir Gudjonsson, Sigurjon Axel Jónsson, Jón Jóhannes Stefánsdóttir, Vigdís Fjóla Danielsen, Ragnar Palsdottir, Astridur Jonsson, Hakon Helgason, Agnar Sturla Magnusson, Olafur Thor Thorsteinsdottir, Unnur Björnsson, Hans Tómas Stefansson, Kari Sulem, Patrick Faculty of Medicine Other departments Cardio-Vascular Center Faculty of Sociology, Anthropology and Folkloristics Health Sciences 2023 749912 https://hdl.handle.net/20.500.11815/4508 https://doi.org/10.1038/s41431-023-01455-0 en eng European Journal of Human Genetics; () http://www.scopus.com/inward/record.url?scp=85170083159&partnerID=8YFLogxK Klemenzdottir , E O , Arnadottir , G A , Jensson , B O , Jonasdottir , A , Katrinardottir , H , Fridriksdottir , R , Jonasdottir , A , Sigurdsson , A , Gudjonsson , S A , Jónsson , J J , Stefánsdóttir , V F , Danielsen , R , Palsdottir , A , Jonsson , H , Helgason , A S , Magnusson , O T , Thorsteinsdottir , U , Björnsson , H T , Stefansson , K & Sulem , P 2023 , ' A population-based survey of FBN1 variants in Iceland reveals underdiagnosis of Marfan syndrome ' , European Journal of Human Genetics . https://doi.org/10.1038/s41431-023-01455-0 1018-4813 188795717 154975de-22ed-49cc-a43f-c5516cd71978 85170083159 https://hdl.handle.net/20.500.11815/4508 doi:10.1038/s41431-023-01455-0 info:eu-repo/semantics/openAccess Barnalæknisfræði Lífefna- og sameindalíffræði Náttúrufræðingar Hjartalæknisfræði Genetics Genetics (clinical) /dk/atira/pure/researchoutput/researchoutputtypes/contributiontojournal/article 2023 ftopinvisindi https://doi.org/20.500.11815/450810.1038/s41431-023-01455-0 2023-11-01T23:55:30Z Publisher Copyright: © 2023, The Author(s). Marfan syndrome (MFS) is an autosomal dominant condition characterized by aortic aneurysm, skeletal abnormalities, and lens dislocation, and is caused by variants in the FBN1 gene. To explore causes of MFS and the prevalence of the disease in Iceland we collected information from all living individuals with a clinical diagnosis of MFS in Iceland (n = 32) and performed whole-genome sequencing of those who did not have a confirmed genetic diagnosis (27/32). Moreover, to assess a potential underdiagnosis of MFS in Iceland we attempted a genotype-based approach to identify individuals with MFS. We interrogated deCODE genetics’ database of 35,712 whole-genome sequenced individuals to search for rare sequence variants in FBN1. Overall, we identified 15 pathogenic or likely pathogenic variants in FBN1 in 44 individuals, only 22 of whom were previously diagnosed with MFS. The most common of these variants, NM_000138.4:c.8038 C > T p.(Arg2680Cys), is present in a multi-generational pedigree, and was found to stem from a single forefather born around 1840. The p.(Arg2680Cys) variant associates with a form of MFS that seems to have an enrichment of abdominal aortic aneurysm, suggesting that this may be a particularly common feature of p.(Arg2680Cys)-associated MFS. Based on these combined genetic and clinical data, we show that MFS prevalence in Iceland could be as high as 1/6,600 in Iceland, compared to 1/10,000 based on clinical diagnosis alone, which indicates underdiagnosis of this actionable genetic disorder. Peer reviewed Article in Journal/Newspaper Iceland Opin vísindi (Iceland) European Journal of Human Genetics |
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Opin vísindi (Iceland) |
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ftopinvisindi |
language |
English |
topic |
Barnalæknisfræði Lífefna- og sameindalíffræði Náttúrufræðingar Hjartalæknisfræði Genetics Genetics (clinical) |
spellingShingle |
Barnalæknisfræði Lífefna- og sameindalíffræði Náttúrufræðingar Hjartalæknisfræði Genetics Genetics (clinical) Klemenzdottir, Elin Ola Arnadottir, Gudny A Jensson, Brynjar Orn Jonasdottir, Adalbjorg Katrinardottir, Hildigunnur Fridriksdottir, Run Jonasdottir, Aslaug Sigurdsson, Asgeir Gudjonsson, Sigurjon Axel Jónsson, Jón Jóhannes Stefánsdóttir, Vigdís Fjóla Danielsen, Ragnar Palsdottir, Astridur Jonsson, Hakon Helgason, Agnar Sturla Magnusson, Olafur Thor Thorsteinsdottir, Unnur Björnsson, Hans Tómas Stefansson, Kari Sulem, Patrick A population-based survey of FBN1 variants in Iceland reveals underdiagnosis of Marfan syndrome |
topic_facet |
Barnalæknisfræði Lífefna- og sameindalíffræði Náttúrufræðingar Hjartalæknisfræði Genetics Genetics (clinical) |
description |
Publisher Copyright: © 2023, The Author(s). Marfan syndrome (MFS) is an autosomal dominant condition characterized by aortic aneurysm, skeletal abnormalities, and lens dislocation, and is caused by variants in the FBN1 gene. To explore causes of MFS and the prevalence of the disease in Iceland we collected information from all living individuals with a clinical diagnosis of MFS in Iceland (n = 32) and performed whole-genome sequencing of those who did not have a confirmed genetic diagnosis (27/32). Moreover, to assess a potential underdiagnosis of MFS in Iceland we attempted a genotype-based approach to identify individuals with MFS. We interrogated deCODE genetics’ database of 35,712 whole-genome sequenced individuals to search for rare sequence variants in FBN1. Overall, we identified 15 pathogenic or likely pathogenic variants in FBN1 in 44 individuals, only 22 of whom were previously diagnosed with MFS. The most common of these variants, NM_000138.4:c.8038 C > T p.(Arg2680Cys), is present in a multi-generational pedigree, and was found to stem from a single forefather born around 1840. The p.(Arg2680Cys) variant associates with a form of MFS that seems to have an enrichment of abdominal aortic aneurysm, suggesting that this may be a particularly common feature of p.(Arg2680Cys)-associated MFS. Based on these combined genetic and clinical data, we show that MFS prevalence in Iceland could be as high as 1/6,600 in Iceland, compared to 1/10,000 based on clinical diagnosis alone, which indicates underdiagnosis of this actionable genetic disorder. Peer reviewed |
author2 |
Faculty of Medicine Other departments Cardio-Vascular Center Faculty of Sociology, Anthropology and Folkloristics Health Sciences |
format |
Article in Journal/Newspaper |
author |
Klemenzdottir, Elin Ola Arnadottir, Gudny A Jensson, Brynjar Orn Jonasdottir, Adalbjorg Katrinardottir, Hildigunnur Fridriksdottir, Run Jonasdottir, Aslaug Sigurdsson, Asgeir Gudjonsson, Sigurjon Axel Jónsson, Jón Jóhannes Stefánsdóttir, Vigdís Fjóla Danielsen, Ragnar Palsdottir, Astridur Jonsson, Hakon Helgason, Agnar Sturla Magnusson, Olafur Thor Thorsteinsdottir, Unnur Björnsson, Hans Tómas Stefansson, Kari Sulem, Patrick |
author_facet |
Klemenzdottir, Elin Ola Arnadottir, Gudny A Jensson, Brynjar Orn Jonasdottir, Adalbjorg Katrinardottir, Hildigunnur Fridriksdottir, Run Jonasdottir, Aslaug Sigurdsson, Asgeir Gudjonsson, Sigurjon Axel Jónsson, Jón Jóhannes Stefánsdóttir, Vigdís Fjóla Danielsen, Ragnar Palsdottir, Astridur Jonsson, Hakon Helgason, Agnar Sturla Magnusson, Olafur Thor Thorsteinsdottir, Unnur Björnsson, Hans Tómas Stefansson, Kari Sulem, Patrick |
author_sort |
Klemenzdottir, Elin Ola |
title |
A population-based survey of FBN1 variants in Iceland reveals underdiagnosis of Marfan syndrome |
title_short |
A population-based survey of FBN1 variants in Iceland reveals underdiagnosis of Marfan syndrome |
title_full |
A population-based survey of FBN1 variants in Iceland reveals underdiagnosis of Marfan syndrome |
title_fullStr |
A population-based survey of FBN1 variants in Iceland reveals underdiagnosis of Marfan syndrome |
title_full_unstemmed |
A population-based survey of FBN1 variants in Iceland reveals underdiagnosis of Marfan syndrome |
title_sort |
population-based survey of fbn1 variants in iceland reveals underdiagnosis of marfan syndrome |
publishDate |
2023 |
url |
https://hdl.handle.net/20.500.11815/4508 https://doi.org/10.1038/s41431-023-01455-0 |
genre |
Iceland |
genre_facet |
Iceland |
op_relation |
European Journal of Human Genetics; () http://www.scopus.com/inward/record.url?scp=85170083159&partnerID=8YFLogxK Klemenzdottir , E O , Arnadottir , G A , Jensson , B O , Jonasdottir , A , Katrinardottir , H , Fridriksdottir , R , Jonasdottir , A , Sigurdsson , A , Gudjonsson , S A , Jónsson , J J , Stefánsdóttir , V F , Danielsen , R , Palsdottir , A , Jonsson , H , Helgason , A S , Magnusson , O T , Thorsteinsdottir , U , Björnsson , H T , Stefansson , K & Sulem , P 2023 , ' A population-based survey of FBN1 variants in Iceland reveals underdiagnosis of Marfan syndrome ' , European Journal of Human Genetics . https://doi.org/10.1038/s41431-023-01455-0 1018-4813 188795717 154975de-22ed-49cc-a43f-c5516cd71978 85170083159 https://hdl.handle.net/20.500.11815/4508 doi:10.1038/s41431-023-01455-0 |
op_rights |
info:eu-repo/semantics/openAccess |
op_doi |
https://doi.org/20.500.11815/450810.1038/s41431-023-01455-0 |
container_title |
European Journal of Human Genetics |
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1782335512156045312 |