Factor V (FV) deficiency is a rare autosomal recessive haemorrhagic disorder associated with moderate to severe bleeding symptoms. Conventional mutational screening leads to a complete molecular genetic diagnosis only in about 80-90% of cases. Large gene rearrangements, which could explain at least part of the "missing alleles" have not been reported so far in FV-deficient patients. In this work, we investigated a family with hereditary FV deficiency, in which the proband is compound heterozygous for a 205-Kb deletion, involving the first seven exons of F5, and the entire selectin P, L, and E genes, and for a novel splicing mutation (IVS12+5G>A). The deletion breakpoints, determined by using a combination of semi-quantitative real-time PCR and long PCR assays, occurred within AluY repeat sequences, suggesting an Alu-mediated unequal homologous recombination as the mechanism responsible for the deletion. The in vitro characterisation of the IVS12+5G>A mutation demonstrated that this mutation causes the skipping of exon 12 and the activation of a cryptic splice site. Low levels of residual wild-type splicing were also detectable, in agreement with the notion that the complete absence of FV may be not compatible with life. © Schattauer 2011.
Identification of the first alu-mediated large deletion involving the f5 gene in a compound heterozygous patient with severe factor v deficiency / I. Guella, E.M. Paraboschi, W.A. van Schalkwyk, R. Asselta, S. Duga. - In: THROMBOSIS AND HAEMOSTASIS. - ISSN 0340-6245. - 106:2(2011 Aug), pp. 296-303.
|Titolo:||Identification of the first alu-mediated large deletion involving the f5 gene in a compound heterozygous patient with severe factor v deficiency|
GUELLA, ILARIA (Primo)
PARABOSCHI, ELVEZIA MARIA (Secondo)
ASSELTA, ROSANNA (Penultimo)
DUGA, STEFANO (Corresponding)
|Parole Chiave:||Alu sequence; Coagulation factor V; Factor V deficiency; Large deletion; Splicing mutation|
|Settore Scientifico Disciplinare:||Settore BIO/11 - Biologia Molecolare|
|Data di pubblicazione:||ago-2011|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1160/TH11-03-0149|
|Appare nelle tipologie:||01 - Articolo su periodico|