Premium
Pseudo‐exon activation caused by a deep‐intronic mutation in the fibrinogen γ ‐chain gene as a novel mechanism for congenital afibrinogenaemia
Author(s) -
Spena Silvia,
Asselta Rosanna,
Platé Manuela,
Castaman Giancarlo,
Duga Stefano,
Tenchini Maria Luisa
Publication year - 2007
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2007.06758.x
Subject(s) - exon , genetics , intron , proband , mutation , rna splicing , biology , gene , splice , coding region , splice site mutation , microbiology and biotechnology , alternative splicing , rna
Summary 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.