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Thromb Haemost 2001; 86(01): 154-163
DOI: 10.1055/s-0037-1616213
Research Article
Schattauer GmbH

The Molecular Basis of Inherited Afibrinogenaemia

Marguerite Neerman-Arbez
1   Division of Medical Genetics, University Medical School, Geneva, Switzerland
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Publication Date:
12 December 2017 (online)

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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
 

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