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) |