Summary
This article reviews the substantial progress made in understanding the molecular
basis of inherited afibrinogenaemia (or congenital afibrinogenaemia), an autosomal
recessive disorder characterised by the complete absence of detectable fibrinogen.
The identification in 1999 of the first genetic defect, recurrent homozygous deletions
of approximately 11 kb of the fibrinogen alpha-chain (FGA) gene, revealed that the disease was caused by defective fibrinogen synthesis, and
led to the subsequent analysis of the three fibrinogen genes in other affected individuals
with the identification of numerous causative mutations. Combined analyses of more
than thirty unrelated afibrinogenaemia families from various ethnic groups have shown
that the majority of patients have truncating mutations in the FGA gene although intuitively all three fibrinogen genes might be equally implicated.
These results will facilitate molecular diagnosis of the disorder, permit prenatal
diagnosis for families who so desire, and pave the way for new therapeutic approaches
such as gene therapy.
Key words
Fibrinogen - mutations - recurrence - splicing - geographical distribution
