Clinical and molecular characterisation of 21 patients affected by quantitative fibrinogen deficiency
Articolo
Data di Pubblicazione:
2015
Citazione:
Clinical and molecular characterisation of 21 patients affected by quantitative fibrinogen deficiency / R. Asselta, M. Platé, M. Robusto, M. Borhany, I. Guella, G. Soldà, A. Afrasiabi, M. Menegatti, T. Shamsi, F. Peyvandi, S. Duga. - In: THROMBOSIS AND HAEMOSTASIS. - ISSN 0340-6245. - 113:3(2015 Mar), pp. 567-576. [10.1160/TH14-07-0629]
Abstract:
Fibrinogen is a plasma glycoprotein mainly synthesised by hepatocytes
and circulating as a 340-kDa hexamer consisting of two sets of
three different polypeptide chains (A , B , and , encoded by the FGA,
FGB, and FGG gene, respectively). Congenital afibrinogenaemia and
hypofibrinogenaemia are rare bleeding disorders characterised by abnormally
low levels of functional and immunoreactive fibrinogen in
plasma, associated with haemorrhagic manifestations of variable severity.
While afibrinogenaemia is caused by mutations in the homozygous
or compound heterozygous state in one of the three fibrinogen
genes, hypofibrinogenaemia is generally due to heterozygous mutations,
and is usually characterised by a milder phenotype. The mutational
spectrum of these quantitative fibrinogen disorders includes
large deletions, point mutations causing premature termination codons,
and missense mutations often affecting fibrinogen assembly
and/or secretion. Here we report the clinical and molecular characterisation
of 13 unrelated afibrinogenaemic and eight hypofibrino -
genaemic patients, leading to the identification of 17 different mutations
(10 hitherto unknown). All the newly-identified missense and
splicing mutations were in vitro expressed to verify their pathogenic
role. Our data increase the number of mutations causing quantitative
fibrinogen deficiencies by about 7 %. The high number of private mutations
identified in the analysed probands indicates that the full mutational
screening of the three fibrinogen genes is still required for
molecular diagnosis.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
Afibrinogenaemia; hypofibrinogenaemia; mutational screening; expression experiments
Elenco autori:
R. Asselta, M. Platé, M. Robusto, M. Borhany, I. Guella, G. Soldà, A. Afrasiabi, M. Menegatti, T. Shamsi, F. Peyvandi, S. Duga
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