title: Sixteen novel hemophilia A causative mutations in the first Argentinian series of severe molecular defects.
abstract: Hemophilia A (HA) is caused by heterogeneous mutations in the factor VIII gene (F8). This paper reports 16 novel small F8-mutations and rearrangements in a series of 80 Argentinian families with severe-HA. Using an updated scheme for F8-analysis, we found 37 F8-inversions (46%), 10 large deletions (13%), 13 small ins/del (16%), 7 nonsense (9%) and 8 missense mutations (10%), including 4 new ones (p.T233K, p.W1942R, p.L2297P and p.L2301S). The potential changes leading to severe-HA of these latter mutations were suggested by bioinformatics. The F8-mutation was characterised in 76 families (95%). They received genetic counselling and precise information about treatment design.
authors.affiliation: Instituto de Investigaciones Hematológicas Mariano R. Castex, Academia Nacional de Medicina de Buenos Aires, Argentina. rossetti@hematologia.anm.edu.ar
authors.forename: Liliana C
authors.initials: LC
authors.lastname: Rossetti
authors.forename: Claudia Pamela
authors.initials: CP
authors.lastname: Radic
authors.forename: Miguel
authors.initials: M
authors.lastname: Candela
authors.forename: Raúl
authors.initials: R
authors.lastname: Pérez Bianco
authors.forename: Miguel
authors.initials: M
authors.lastname: de Tezanos Pinto
authors.forename: Anne
authors.initials: A
authors.lastname: Goodeve
authors.forename: Irene B
authors.initials: IB
authors.lastname: Larripa
authors.forename: Carlos D
authors.initials: CD
authors.lastname: De Brasi
mesh_terms: D001118:Argentina; D019295:Computational Biology; D005169:Factor VIII / Q000235:genetics*; D005192:Family Health; D005260:Female; D015321:Gene Rearrangement; D005817:Genetic Counseling; D006467:Hemophilia A / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D008297:Male; D017720:Molecular Epidemiology; D009154:Mutation
chemical_list: D005169:Factor VIII