Tandem inversion duplication within F8 Intron 1 associated with mild XXXX .

@entity1 @entity2801 @entity7062 @entity49577 @entity447
UNASSIGNED: In approximately 90% of mild @entity447 ( @entity447 ) @entity1 , a missense mutation can be identified using complete gene sequencing. In this study, multiplex ligation-dependent probe amplification analysis was performed as a second step in 10 French-speaking Belgian with mild @entity447 presenting no detectable causal mutation by complete sequencing of the @entity2801 ( @entity2801 ) (F8) gene's 26 exons and its 1.2  kb of contiguous promoter sequence. This gene dosage technique enabled the detection of exon 1 duplications of F8 in three apparently unrelated subjects. Using array-comparative genomic hybridization, breakpoint analysis delimited the duplication extent to 210  kb in the F8 intron 1 and @entity49577 gene intragenic position. We postulated that the rearrangement responsible for this duplication, never before reported, could be attributed to a symmetrical tandem inversion duplication, resulting in a large 233  kb rearrangement of F8 intron 1. This rearranged intron should lead to the production of a small number of normal mRNA transcripts in relation to the mild @entity447 phenotype. Our analysis of the entire F8 mRNA from index case 1, particularly the segment containing exons 1-9, revealed normal amplification and sequencing. Reduced plasma @entity2801 antigen levels caused by cross-reacting material is associated with a quantitative deficiency of plasma @entity2801 . Male @entity1 were unresponsive to @entity7062 ( @entity7062 ). All @entity1 displayed identical F8 haplotypes, despite not being related, which suggests a possible founder effect caused by a 210  kb duplication involving F8 exon 1.
