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COPA syndrome in an Icelandic family caused by a recurrent missense mutation in COPA

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dc.contributor Háskóli Íslands
dc.contributor University of Iceland
dc.contributor.author Jensson, Brynjar Örn
dc.contributor.author Hansdottir, Sif
dc.contributor.author Arnadottir, Gudny
dc.contributor.author Sulem, Gerald
dc.contributor.author Kristjansson, Ragnar
dc.contributor.author Oddsson, Asmundur
dc.contributor.author Benonisdottir, Stefania
dc.contributor.author Jónsson, Hákon
dc.contributor.author Helgason, Agnar
dc.contributor.author Sæmundsdóttir, Jóna
dc.contributor.author Magnússon, Ólafur T.
dc.contributor.author Másson, Gísli
dc.contributor.author Thorisson, Gudmundur
dc.contributor.author Jónasdóttir, Aðalbjörg
dc.contributor.author Jónasdóttir, Áslaug
dc.contributor.author Sigurðsson, Ásgeir
dc.contributor.author Jonsdottir, Ingileif
dc.contributor.author Pétursdóttir, Vigdís
dc.contributor.author Kristinsson, Jón R.
dc.contributor.author Gudbjartsson, Daniel
dc.contributor.author Thorsteinsdottir, Unnur
dc.contributor.author Arngrimsson, Reynir
dc.contributor.author sulem, patrick
dc.contributor.author Guðmundsson, Gunnar
dc.contributor.author Stefansson, Kari
dc.date.accessioned 2017-12-05T10:44:11Z
dc.date.available 2017-12-05T10:44:11Z
dc.date.issued 2017-11-14
dc.identifier.citation Jensson, B. O., Hansdottir, S., Arnadottir, G. A., Sulem, G., Kristjansson, R. P., Oddsson, A., . . . Stefansson, K. (2017). COPA syndrome in an Icelandic family caused by a recurrent missense mutation in COPA. BMC Medical Genetics, 18(1), 129. doi:10.1186/s12881-017-0490-8
dc.identifier.issn 1471-2350
dc.identifier.uri https://hdl.handle.net/20.500.11815/470
dc.description.abstract Background: Rare missense mutations in the gene encoding coatomer subunit alpha (COPA) have recently been shown to cause autoimmune interstitial lung, joint and kidney disease, also known as COPA syndrome, under a dominant mode of inheritance. Case presentation: Here we describe an Icelandic family with three affected individuals over two generations with a rare clinical presentation of lung and joint disease and a histological diagnosis of follicular bronchiolitis. We performed whole-genome sequencing (WGS) of the three affected as well as three unaffected members of the family, and searched for rare genotypes associated with disease using 30,067 sequenced Icelanders as a reference population. We assessed all coding and splicing variants, prioritizing variants in genes known to cause interstitial lung disease. We detected a heterozygous missense mutation, p.Glu241Lys, in the COPA gene, private to the affected family members. The mutation occurred de novo in the paternal germline of the index case and was absent from 30,067 Icelandic genomes and 141,353 individuals from the genome Aggregation Database (gnomAD). The mutation occurs within the conserved and functionally important WD40 domain of the COPA protein. Conclusions: This is the second report of the p.Glu241Lys mutation in COPA, indicating the recurrent nature of the mutation. The mutation was reported to co-segregate with COPA syndrome in a large family from the USA with five affected members, and classified as pathogenic. The two separate occurrences of the p.Glu241Lys mutation in cases and its absence from a large number of sequenced genomes confirms its role in the pathogenesis of the COPA syndrome. Keywords: COPA syndrome, Lung disease, Arthritis, Immune dysregulation, Case report
dc.format.extent 129
dc.language.iso en
dc.publisher Springer Nature
dc.relation.ispartofseries BMC Medical Genetics;18(1)
dc.rights info:eu-repo/semantics/openAccess
dc.subject Genetics
dc.subject Erfðagreining
dc.subject Lungnasjúkdómar
dc.subject Erfðafræði
dc.subject Rannsóknir
dc.title COPA syndrome in an Icelandic family caused by a recurrent missense mutation in COPA
dc.type info:eu-repo/semantics/article
dcterms.license This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
dc.description.version Peer Reviewed
dc.identifier.journal BMC Medical Genetics
dc.identifier.doi 10.1186/s12881-017-0490-8
dc.relation.url http://link.springer.com/content/pdf/10.1186/s12881-017-0490-8.pdf
dc.contributor.department Félags- og mannvísindadeild (HÍ)
dc.contributor.department Faculty of Social and Human Sciences (UI)
dc.contributor.department Læknadeild (HÍ)
dc.contributor.department Faculty of Medicine (UI)
dc.contributor.school Félagsvísindasvið (HÍ)
dc.contributor.school School of Social Sciences (UI)
dc.contributor.school Verkfræði- og náttúruvísindasvið (HÍ)
dc.contributor.school School of Engineering and Natural Sciences (UI)
dc.contributor.school Heilbrigðisvísindasvið (HÍ)
dc.contributor.school School of Health Sciences (UI)

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