Reccurrent F8 Intronic Deletion Found in Mild Hemophilia A Causes Alu Exonization.

ABSTRACT: Incorporation of distant intronic sequences in mature mRNA is an underappreciated cause of genetic disease. Several disease-causing pseudoexons have been found to contain repetitive elements such as Alu elements. This study describes an original pathological mechanism by which a small intronic deletion leads to Alu exonization. We identified an intronic deletion, c.2113+461_2113+473del, in the F8 intron 13, in two individuals with mild hemophilia A. In vivo and in vitro transcript analysis found an aberrant transcript, with an insertion of a 122-bp intronic fragment (c.2113_2114ins2113+477_2113+598) at the exon 13-14 junction. This out-of-frame insertion is predicted to lead to truncated protein (p.Gly705Aspfs^∗37). DNA sequencing analysis found that the pseudoexon corresponds to

SUBMITTER: Jourdy Y 

PROVIDER: S-EPMC5985402 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature