Molecular analysis of afibrinogenemic mutations caused by a homozygous FGA1238 bp deletion, and a compound heterozygous FGA1238 bp deletion and novel FGA c.54+3A>C substitution

siRNA down-regulation of FGA mRNA in HepG2 cells demonstrated that heterozygous abnormality of the Aα-chain gene does not affect the plasma fibrinogen level

“…We encountered two afibrinogenemic patients' parents who are heterozygous genetic FGA abnormality and normal levels of plasma fibrinogen [10]. Thus, we hypothesized that in normal liver, FGA mRNA was more than two-fold higher than FGB and/or FGG mRNA, and if FGA mRNA was decreased by almost half by a mutation with FGA mRNA decay, plasma fibrinogen was not decreased and was maintained in the normal range.…”

“…Thus, we hypothesized that in normal liver, FGA mRNA was more than two-fold higher than FGB and/or FGG mRNA, and if FGA mRNA was decreased by almost half by a mutation with FGA mRNA decay, plasma fibrinogen was not decreased and was maintained in the normal range. To examine the hypothesis, we quantitated mRNA levels for three normal livers and a human hepatocyte cell We showed plasma fibrinogen concentration for probands with afibrinogenemia causing homozygote FGAΔ1238bp mutation and compound heterozygotes including FGAΔ1238bp mutation, and their heterozygous family members in Table 1 [10][11][12][13][14]. Plasma fibrinogen levels of all heterozygous individuals were almost normal, and 1 of 16 people had <1.5 g/l by either the functional method or immunological determination method.…”

“…In particular, reports causing large deletions between 1.2 and 15 kb were restricted in FGA [6]. Recently, we identified two afibrinogenemias, caused by homozygous deletion of 1238 bases of the Aα-chain gene (FGAΔ1238) and compound heterozygous deletion of FGAΔ1238 and FGA c.54+3A>C, examined the molecular basis of the lack of protein, and designated them as Yokkaichi and Kurashiki II, respectively [10].…”

“…Six families, including our two cases, with FGAΔ1238 have only been found in Far Eastern countries, one in China [11] and five in Japan [10,[12][13][14], and regarding which parents and family members have a heterozygous genetic abnormality, the plasma fibrinogen concentrations were all normal (Table 1). According to our observation and the coincident reports, we hypothesize these phenomena as follows.…”

Congenital Fibrinogen Disorders: An Update

“…Prolonged bleeding after venous puncture has also been reported. 28 Joint bleeding which is common in patients with severe hemophilia is infrequent: In a series of 72 patients with severe fibrinogen deficiency, hemarthrosis was observed in 25% of cases. 29 Persistent damage to the musculoskeletal system and resulting handicap is also less frequent in patients with afibrinogenemia.…”