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Article scientifique
Anglais

Deletion of the fibrogen alpha-chain gene (FGA) causes congenital afibrogenemia

Publié dansThe Journal of clinical investigation, vol. 103, no. 2, p. 215-218
Date de publication1999
Résumé

Congenital afibrinogenemia is a rare autosomal recessive disorder characterized by the complete absence of detectable fibrinogen. Uncontrolled bleeding after birth from the umbilical cord is common, and spontaneous intracerebral bleeding and splenic rupture can occur throughout life. Patients respond well to fibrinogen replacement therapy, either prophylactically or on demand. Because the half-life of infused fibrinogen is essentially normal, the genetic defect is assumed to be at the level of synthesis, but no responsible locus has been identified. Preliminary studies using Southern blotting suggested that no gross structural changes of the fibrinogen genes were present in patients. We report the identification of causative mutations in a nonconsanguineous Swiss family with congenital afibrinogenemia. The four affected male individuals (two brothers and their two first cousins) have homozygous deletions of approximately 11 kb of the fibrinogen alpha-chain gene (FGA). Haplotype data suggest that these deletions occurred separately, on three distinct ancestral chromosomes, implying that the FGA region of the fibrinogen locus is susceptible to deletion by a common mechanism. Furthermore, our results demonstrate that humans, like mice, may be born without the capacity to synthesize functional fibrinogen.

Mots-clés
  • Afibrinogenemia/ genetics
  • Blotting, Southern
  • Chromosomes, Human, Pair 4/genetics
  • Fibrinogen/ genetics
  • Genetic Markers/genetics
  • Haplotypes/genetics
  • Homozygote
  • Humans
  • Male
  • Pedigree
  • Polymerase Chain Reaction
  • Sequence Deletion/genetics
  • Switzerland
Citation (format ISO)
NEERMAN ARBEZ, Marguerite et al. Deletion of the fibrogen alpha-chain gene (FGA) causes congenital afibrogenemia. In: The Journal of clinical investigation, 1999, vol. 103, n° 2, p. 215–218. doi: 10.1172/JCI5471
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ISSN du journal0021-9738
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