Molecular analysis of the fibrinogen gene cluster in 16 patients with congenital afibrinogenemia: novel truncating mutations in the FGA and FGG genes

Congenital afibrinogenemia is an autosomal recessive disorder characterized by the complete absence of detectable fibrinogen. We previously identified the first causative mutations for this disease in a non-consanguineous Swi ss family. These were homozygous deletions of approximately 11 kb of the fi brinogen alpha chain gene (FGA). Our subsequent study revealed that the maj ority of cases were attributable to truncating mutations in FGA, with the m ost common mutation affecting the donor splice site in FGA intron 4 (IVS4+1 G-->T). Here, we report 13 further unrelated patients with mutations in FG A, confirming the relative importance of this gene compared with FGG and FG B in the molecular aetiology of afibrinogenemia. Three other patients were homozygous for mutations in FGG. Eight novel mutations were identified: fiv e in FGA and three in FGG. Sufficient mutation data is now available to per mit an effective strategy for the genetic diagnosis of congenital afibrinog enemia.