title: Haemophilia A: molecular insights.
abstract: Haemophilia A is the most common inherited bleeding disorder caused by defects in the F8C gene that encodes coagulation factor VIII. This X-linked recessive disorder occurs in approximately 1:5000 males. Haemophilia A is diagnosed based on normal prothrombin time, altered activated partial thromboplastin time and reduced factor VIII activity in plasma. Carrier females are usually asymptomatic and can be identified only by molecular analysis. The most frequent mutations in F8C are intron 22 and 1 inversions, which occur in approximately 50% and 5% of patients, respectively, with a severe phenotype. Large gene deletions are observed in approximately 5% of alleles from patients with severe haemophilia A. The remaining severe cases and all moderate and mild cases result from numerous point mutations and small insertions/deletions, which are de novo mutations in one-third of cases. Thus, molecular diagnosis of carrier status and prenatal diagnosis in families without intron 22 or 1 inversions is based on scanning techniques or gene sequencing. When the disease-causing mutation cannot be identified, molecular diagnosis is performed by linkage analysis of several DNA polymorphic markers linked to F8C. Given the clinical heterogeneity among haemophilic patients, many groups, including our own, have examined the relationships between prothrombotic gene variants and haemophilic phenotype to investigate whether prothrombotic gene variants modify clinical expression of the disease.
authors: Dipartimento di Biochimica e Biotecnologie Mediche, Università di Napoli Federico II, CEINGE-Biotecnologie avanzate and SEMM, Naples, Italy. castaldo@dbbm.unina.it
authors: Giuseppe
authors: G
authors: Castaldo
authors: Valeria
authors: V
authors: D'Argenio
authors: Paola
authors: P
authors: Nardiello
authors: Federica
authors: F
authors: Zarrilli
authors: Veronica
authors: V
authors: Sanna
authors: Angiola
authors: A
authors: Rocino
authors: Antonio
authors: A
authors: Coppola
authors: Giovanni
authors: G
authors: Di Minno
authors: Francesco
authors: F
authors: Salvatore
mesh_terms: D007446:Chromosome Inversion; D006580:Genetic Carrier Screening; D008040:Genetic Linkage; D015316:Genetic Therapy; D006467:Hemophilia A / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000628:therapy; D006801:Humans; D007438:Introns; D009154:Mutation; D011296:Prenatal Diagnosis