Genetic analyses of novel compound heterozygous hypodysfibrinogenemia, Tsukuba I: FGG c.1129Â +Â 62_65 del AATA and FGG c.1299Â +Â 4 del A

Minigene I incorporating the IVS-8 deletion showed two products: a normal splicing product and the unspliced product. Minigene II incorporating the Ex-9 deletion only produced the unspliced product. The established γ′409ΔA-CHO cells secreted variant fibrinogen more effectively than normal fibrinogen. Therefore, the aberrant splicing products derived from the IVS-8 deletion cause hypofibrinogenemia most likely due to nonsense-mediated mRNA decay and the partial production of normal γA- and γ′-chains; moreover, the Ex-9 deletion causes hypodysfibrinogenemia due to the absence of normal γA- and γ′-chain production (hypofibrinogenemia) and augmented aberrant γ′-chain production (dysfibrinogenemia).