title: Inversion mutation as a major cause of severe hemophilia A in Italian patients.
abstract: We investigated the presence of a recombinant event between the F8A gene located in intron 22 of the factor VIII gene and the two additional copies of F8A lying 500 Kb upstream of FVIII in severe hemophilic patients. The genomic DNA of 146 unrelated Italian patients with severe hemophilia A (HA) was hybridized with an F8A gene probe to detect the abnormal band patterns. A recombinant event was found in 71/146 patients, confirming the high incidence of this mutation in the Italian hemophilic population also. We conclude that the high frequency of the mutation in HA subjects allows us to make a direct and safe diagnosis in about 50% of our families without resorting to RFLP analysis.
authors.affiliation: Laboratorio di Ematologia, Istituto G. Gaslini, Genova, Italy.
authors.forename: P G
authors.initials: PG
authors.lastname: Mori
authors.forename: D
authors.initials: D
authors.lastname: Caprino
authors.forename: M P
authors.initials: MP
authors.lastname: Bicocchi
authors.forename: A
authors.initials: A
authors.lastname: Valetto
authors.forename: F
authors.initials: F
authors.lastname: Bottini
authors.forename: M
authors.initials: M
authors.lastname: Aquila
mesh_terms: D000328:Adult; D007446:Chromosome Inversion; D004247:DNA / Q000235:genetics; D004252:DNA Mutational Analysis; D015252:Deoxyribonucleases, Type II Site-Specific; D004587:Electrophoresis, Agar Gel; D005169:Factor VIII / Q000235:genetics*; D005260:Female; D005315:Fetal Diseases / Q000175:diagnosis / Q000235:genetics; D005787:Gene Frequency; D006467:Hemophilia A / Q000175:diagnosis / Q000196:embryology / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D007438:Introns / Q000235:genetics; D007558:Italy / Q000453:epidemiology; D008297:Male; D009693:Nucleic Acid Hybridization; D012150:Polymorphism, Restriction Fragment Length; D011247:Pregnancy; D011296:Prenatal Diagnosis; D014960:X Chromosome / Q000235:genetics* / Q000648:ultrastructure
chemical_list: D005169:Factor VIII; D004247:DNA; C041666:endodeoxyribonuclease BclI; D015252:Deoxyribonucleases, Type II Site-Specific