Mutation of the translation initiation codon in FGA causes congenital afibrinogenemia

Abstract

Congenital afibrinogenemia is characterized by the complete absence of fibrinogen, the precursor of the major protein constituent of the blood clot, fibrin. Extensive allelic heterogeneity has been found for this disorder and more than 40 mutations, the majority in FGA, have been identified in homozygosity or in compound heterozygosity. However, the continuous genetic analysis of additional patients still allows the identification of novel mutations and thus the greater understanding of fibrinogen structure and function. Here we report the identification of a novel missense mutation in FGA exon 1 affecting the translation initiation codon: c.1 A>T (ATG>TTG) M1L, identified in a young boy from Madagascar in compound heterozygosity with a second mutation in FGA exon 4: c.385 C>T (CGA>TGA) R129X. The patient suffered from occasional severe arthralgias (shoulder, knee) most likely caused by intra-articular bleeding with subsequent inflammation.