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Publicação
PROS1 novel splice site variant decreases protein S expression in patients from two families with thrombotic disease
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Orientador(es)
Resumo(s)
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.
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.
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.
Descrição
Palavras-chave
PROS1 Protein S Deficiency Thrombophilia Thrombosis Venous Thromboembolism. Splicing Splice-site Doenças Genéticas
Contexto Educativo
Citação
Clin Case Rep. 2017 Nov 3;5(12):2062-2065. doi: 10.1002/ccr3.1226. eCollection 2017 Dec
Editora
John Wiley & Sons Ltd.