PROS1 novel splice site variant decreases protein S expression in patients from two families with thrombotic disease

Menezes, Juliane; Ventura, Célia; Matos Costa, João; Parreira, Elsa; Romão, Luísa; Gonçalves, João

Publication

PROS1 novel splice site variant decreases protein S expression in patients from two families with thrombotic disease

2017-11-03Journal article

dc.contributor.author	Menezes, Juliane
dc.contributor.author	Ventura, Célia
dc.contributor.author	Matos Costa, João
dc.contributor.author	Parreira, Elsa
dc.contributor.author	Romão, Luísa
dc.contributor.author	Gonçalves, João
dc.date.accessioned	2018-03-01T17:33:28Z
dc.date.available	2018-03-01T17:33:28Z
dc.date.issued	2017-11-03
dc.description.abstract	Protein S (PS) is a widely studied protein with an important function in the downregulation of thrombin formation. Since its discovery in 1976, more than 400 variants have been described in PS gene (PROS1) associated with PS deficiency and as a risk factor for venous thromboembolism (VTE). We describe a novel variant, c.1871-14T>G, in intron 14 of PROS1 gene identified in two patients with PS deficiency from two unrelated families with a history of thrombotic disease. This alteration leads to a PROS1 mRNA expression reduction, probably due to nonsense-mediated mRNA decay. Our results suggest that c.1871-14T>G is causative of type I PS deficiency in these patients, highlighting the importance of screening not only the coding and the most conserved intron–exon junctions, but also perform mRNA-based studies. We call attention to the potential increased risk of VTE in hereditary type I PS deficiency associated with this cryptic splice-site variant.	pt_PT
dc.description.abstract	Key Clinical Message: Our results prove that c.1871-14T>G is causative of type I PS deficiency, highlighting the importance of performing mRNA-based studies in order to evaluate variants pathogenicity. We evidence the increased risk of venous thromboembolism associated with this cryptic splice-site variant if present in patients with PS deficiency.	pt_PT
dc.description.sponsorship	Juliane Menezes is supported by a fellowship from Fundação para a Ciência e a Tecnologia (SFRH/BPD/98360/2013), and this work was partially funded by the Centre for Toxicogenomics and Human Health—ToxOmics, Genetics, Oncology and Human Toxicology from Fundação para a Ciência e a Tecnologia (UID/BIM/00009/2013).	pt_PT
dc.description.version	info:eu-repo/semantics/publishedVersion	pt_PT
dc.identifier.citation	Clin Case Rep. 2017 Nov 3;5(12):2062-2065. doi: 10.1002/ccr3.1226. eCollection 2017 Dec	pt_PT
dc.identifier.doi	10.1002/ccr3.1226	pt_PT
dc.identifier.issn	2050-0904
dc.identifier.uri	http://hdl.handle.net/10400.18/5109
dc.language.iso	eng	pt_PT
dc.peerreviewed	yes	pt_PT
dc.publisher	John Wiley & Sons Ltd.	pt_PT
dc.relation.publisherversion	http://onlinelibrary.wiley.com/doi/10.1002/ccr3.1226/full	pt_PT
dc.rights.uri	http://creativecommons.org/licenses/by/4.0/	pt_PT
dc.subject	PROS1	pt_PT
dc.subject	Protein S Deficiency	pt_PT
dc.subject	Thrombophilia	pt_PT
dc.subject	Thrombosis	pt_PT
dc.subject	Venous Thromboembolism.	pt_PT
dc.subject	Splicing	pt_PT
dc.subject	Splice-site	pt_PT
dc.subject	Doenças Genéticas	pt_PT
dc.title	PROS1 novel splice site variant decreases protein S expression in patients from two families with thrombotic disease	pt_PT
dc.type	journal article
dspace.entity.type	Publication
oaire.awardURI	info:eu-repo/grantAgreement/FCT/5876/UID%2FBIM%2F00009%2F2013/PT
oaire.citation.endPage	2065	pt_PT
oaire.citation.issue	12	pt_PT
oaire.citation.startPage	2062	pt_PT
oaire.citation.title	Clinical Case Reports	pt_PT
oaire.citation.volume	5	pt_PT
oaire.fundingStream	5876
project.funder.identifier	http://doi.org/10.13039/501100001871
project.funder.name	Fundação para a Ciência e a Tecnologia
rcaap.rights	openAccess	pt_PT
rcaap.type	article	pt_PT
relation.isProjectOfPublication	e9cc9728-4f09-4e3a-b30d-53d4429986fb
relation.isProjectOfPublication.latestForDiscovery	e9cc9728-4f09-4e3a-b30d-53d4429986fb