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A population-based survey of FBN1 variants in Iceland reveals underdiagnosis of Marfan syndrome

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dc.contributor.author Klemenzdottir, Elin Ola
dc.contributor.author Arnadottir, Gudny A
dc.contributor.author Jensson, Brynjar Orn
dc.contributor.author Jonasdottir, Adalbjorg
dc.contributor.author Katrinardottir, Hildigunnur
dc.contributor.author Fridriksdottir, Run
dc.contributor.author Jonasdottir, Aslaug
dc.contributor.author Sigurdsson, Asgeir
dc.contributor.author Gudjonsson, Sigurjon Axel
dc.contributor.author Jónsson, Jón Jóhannes
dc.contributor.author Stefánsdóttir, Vigdís Fjóla
dc.contributor.author Danielsen, Ragnar
dc.contributor.author Palsdottir, Astridur
dc.contributor.author Jonsson, Hakon
dc.contributor.author Helgason, Agnar Sturla
dc.contributor.author Magnusson, Olafur Thor
dc.contributor.author Thorsteinsdottir, Unnur
dc.contributor.author Björnsson, Hans Tómas
dc.contributor.author Stefansson, Kari
dc.contributor.author Sulem, Patrick
dc.date.accessioned 2023-10-21T01:07:57Z
dc.date.available 2023-10-21T01:07:57Z
dc.date.issued 2023
dc.identifier.citation 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
dc.identifier.issn 1018-4813
dc.identifier.other 188795717
dc.identifier.other 154975de-22ed-49cc-a43f-c5516cd71978
dc.identifier.other 85170083159
dc.identifier.uri https://hdl.handle.net/20.500.11815/4508
dc.description Publisher Copyright: © 2023, The Author(s).
dc.description.abstract 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.
dc.format.extent 749912
dc.language.iso en
dc.relation.ispartofseries European Journal of Human Genetics; ()
dc.rights info:eu-repo/semantics/openAccess
dc.subject Barnalæknisfræði
dc.subject Lífefna- og sameindalíffræði
dc.subject Náttúrufræðingar
dc.subject Hjartalæknisfræði
dc.subject Genetics
dc.subject Genetics (clinical)
dc.title A population-based survey of FBN1 variants in Iceland reveals underdiagnosis of Marfan syndrome
dc.type /dk/atira/pure/researchoutput/researchoutputtypes/contributiontojournal/article
dc.description.version Peer reviewed
dc.identifier.doi 10.1038/s41431-023-01455-0
dc.relation.url http://www.scopus.com/inward/record.url?scp=85170083159&partnerID=8YFLogxK
dc.contributor.department Faculty of Medicine
dc.contributor.department Other departments
dc.contributor.department Cardio-Vascular Center
dc.contributor.department Faculty of Sociology, Anthropology and Folkloristics
dc.contributor.school Health Sciences

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