title: Pseudo-exon activation caused by a deep-intronic mutation in the fibrinogen gamma-chain gene as a novel mechanism for congenital afibrinogenaemia.
abstract: Congenital afibrinogenaemia, characterized by severe fibrinogen deficiency, is caused by mutations within FGA, FGB or FGG. Conventional sequencing of coding regions and splice signals of these three genes did not reveal any mutation in an afibrinogenaemic proband. After confirming disease co-segregation with the fibrinogen cluster, full intron sequencing was tackled leading to the identification of a novel transvertion within FGG intron 6 (IVS6-320A-->T). Its effect on mRNA processing was evaluated in-vitro: the in-frame inclusion of a 75-bp pseudo-exon carrying a premature stop was found, representing the first report of pseudo-exon activation as a mechanism leading to afibrinogenaemia.
authors.affiliation: Department of Biology and Genetics for Medical Sciences, University of Milan, Milan, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Spena
authors.forename: Rosanna
authors.initials: R
authors.lastname: Asselta
authors.forename: Manuela
authors.initials: M
authors.lastname: Platé
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Castaman
authors.forename: Stefano
authors.initials: S
authors.lastname: Duga
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Tenchini
mesh_terms: D000347:Afibrinogenemia / Q000151:congenital* / Q000235:genetics*; D017398:Alternative Splicing; D018388:Codon, Terminator; D004252:DNA Mutational Analysis; D004591:Electrophoresis, Polyacrylamide Gel; D005091:Exons; D005260:Female; D005340:Fibrinogen / Q000235:genetics*; D006801:Humans; D007438:Introns; D008297:Male; D009154:Mutation; D010375:Pedigree
chemical_list: D018388:Codon, Terminator; D005340:Fibrinogen