Pseudo-exon activation caused by a deep-intronic mutation in the fibrinogen gamma-chain gene as a novel mechanism for congenital afibrinogenaemia.
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.
Spena
Silvia
S
Department of Biology and Genetics for Medical Sciences, University of Milan, Milan, Italy.
Asselta
Rosanna
R
Platé
Manuela
M
Castaman
Giancarlo
G
Duga
Stefano
S
Tenchini
Maria Luisa
ML
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
D018388:Codon, Terminator; D005340:Fibrinogen