title: Mutation analysis impact on the genetic counseling of sporadic hemophilia B families.
abstract: Previous studies have shown that hemophilia B (HB) is the result of several different mutations, mostly single nucleotide substitutions, in the factor IX (FIX) gene. In order to evaluate the impact of mutation analysis on genetic counseling in sporadic and uninformative HB familial pedigrees, we re-analyzed by the conformation sensitive gel electrophoresis (CSGE) technique 14 patients, previously studied by restriction fragment length polymorphisms (RFLPs). A single mutation was present within the FIX gene of each patient: 12 mutations were single base substitutions, 1 was a base insertion, and 1 was a four nucleotide deletion; 4/12 mutations have not been described so far. By identifying the detrimental mutations in affected males, carrier status was correctly diagnosed in all the women we studied; 3/12 de novo events were found in maternal meioses with a 25% mutation rate. Identification of the genetic defect was also successfully applied to three prenatal diagnoses.
authors.affiliation: Hemostasis and Hemophilia Laboratory, IV Pediatric Department, G. Gaslini Institute, Genova, Italy. patriziabicocchi@ospedale-gaslini.ge.it
authors.forename: Maria Patrizia
authors.initials: MP
authors.lastname: Bicocchi
authors.forename: Mirella
authors.initials: M
authors.lastname: Pasino
authors.forename: Federico
authors.initials: F
authors.lastname: Bottini
authors.forename: Tiziana
authors.initials: T
authors.lastname: Lanza
authors.forename: Pier Giorgio
authors.initials: PG
authors.lastname: Mori
authors.forename: Maura
authors.initials: M
authors.lastname: Acquila
mesh_terms: D004252:DNA Mutational Analysis; D004591:Electrophoresis, Polyacrylamide Gel; D005164:Factor IX / Q000235:genetics*; D005260:Female; D005817:Genetic Counseling; D002836:Hemophilia B / Q000175:diagnosis* / Q000235:genetics*; D006801:Humans; D007558:Italy; D008297:Male; D010375:Pedigree; D012150:Polymorphism, Restriction Fragment Length
chemical_list: D005164:Factor IX