Understanding the Impact of Aberrant Splicing in Coagulation Factor V Deficiency

International Journal of Molecular Sciences
Elvezia Maria ParaboschiRosanna Asselta

Abstract

Rare inherited coagulation disorders (RICDs) are congenital deficiencies of the plasma proteins that are involved in blood coagulation, which generally lead to lifelong bleeding manifestations. These diseases are generally qualitative and/or quantitative defects that are associated with monoallelic or biallelic mutations in the relevant gene. Among RICDs, factor V (FV) deficiency is one of the least characterized at the molecular level. Here, we investigated four unrelated patients with reduced plasma FV levels (three severe, one mild), which were associated with a moderately severe bleeding tendency. Sequence analysis of the FV gene identified seven different variants, five hitherto unknown (p.D1669G, c.5789-11C>A, c.5789-12C>A, c.5789-5T>G, and c.6528G>C), and two previously reported (c.158+1G>A and c.5789G>A). The possible pathogenic role of the newly identified missense variant was studied by in silico approaches. The remaining six genetic defects (all putative splicing mutations) were investigated for their possible effects on pre-mRNA splicing by transient transfection experiments in HeLa cells with plasmids expressing appropriate hybrid minigenes. The preparation of minigene constructs was instrumental to demonstrate tha...Continue Reading

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Citations

Mar 27, 2021·Blood Coagulation & Fibrinolysis : an International Journal in Haemostasis and Thrombosis·Satish MaharajRajiv Pruthi

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Methods Mentioned

BETA
PCR
transfections

Software Mentioned

Human Splicing Finder
CLUSTAL Omega
Splice Site Prediction Neural Network
ADA
Pdb Viewer
Swiss
PolyPhen2
GnomAD
SIFT
Variant Reporter

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