COPA syndrome in an Icelandic family caused by a recurrent missense mutation in COPA
| Autor: | Olafur Th Magnusson, Agnar Helgason, Gisli Masson, Adalbjorg Jonasdottir, Gudny A. Arnadottir, Ingileif Jonsdottir, Hakon Jonsson, Jona Saemundsdottir, Aslaug Jonasdottir, Gunnar Gudmundsson, Sif Hansdottir, Reynir Arngrímsson, Asgeir Sigurdsson, Gudmundur A. Thorisson, Ragnar P. Kristjansson, Stefania Benonisdottir, Patrick Sulem, Daniel F. Gudbjartsson, Unnur Thorsteinsdottir, Jon R. Kristinsson, Vigdis Petursdottir, Asmundur Oddsson, Kari Stefansson, Brynjar O. Jensson, Gerald Sulem |
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| Přispěvatelé: | Félags- og mannvísindadeild (HÍ), Faculty of Social and Human Sciences (UI), Læknadeild (HÍ), Faculty of Medicine (UI), Félagsvísindasvið (HÍ), School of Social Sciences (UI), Verkfræði- og náttúruvísindasvið (HÍ), School of Engineering and Natural Sciences (UI), Heilbrigðisvísindasvið (HÍ), School of Health Sciences (UI), Háskóli Íslands, University of Iceland |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
COPA syndrome Lung Diseases Male lcsh:Internal medicine Erfðagreining lcsh:QH426-470 Iceland Mutation Missense Case Report Biology Genome Coatomer Protein Germline 03 medical and health sciences 0302 clinical medicine Genotype Genetics Missense mutation Erfðafræði Humans lcsh:RC31-1245 Child Index case Gene Genetics (clinical) 030203 arthritis & rheumatology Lungnasjúkdómar Arthritis Immunologic Deficiency Syndromes Infant Rannsóknir Pedigree lcsh:Genetics Immune dysregulation 030104 developmental biology Lung disease Child Preschool Mutation (genetic algorithm) RNA splicing Female Genome-Wide Association Study |
| Zdroj: | BMC Medical Genetics BMC Medical Genetics, Vol 18, Iss 1, Pp 1-5 (2017) |
| ISSN: | 1471-2350 |
| Popis: | 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 |
| Databáze: | OpenAIRE |
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