title: The Canadian "National Program for hemophilia mutation testing" database: a ten-year review.
abstract: A reference genotyping laboratory was established in 2000 at Queen's University, Kingston, to provide genetic testing for Hemophilia A (HA) and B (HB) and create a Canadian mutation database. Canadian hemophilia treatment centers and genetics clinics provided DNA and clinical information from November 2000 to March 2011. The factor VIII (F8) gene was analyzed in 1,177 patients (47% of HA population) and 787 female family members and the factor IX (F9) gene in 267 patients (47% of HB population) and 123 female family members, using Southern Blot, PCR, conformation sensitive gel electrophoresis, and/or direct sequencing. The mutation detection rates for HA and HB were 91% and 94%, respectively. 380 different F8 mutations were identified: inversions of intron 22 and intron 1, 229 missense, 45 nonsense, eight deletions, 70 frameshifts, 25 splice site, and one compound mutation with a splice site and intron 1 inversion. Of these mutations, 228 were novel to the Hemophilia A Database (HADB, http://hadb.org.uk/). A total 125 different F9 mutations were identified: 80 missense, 12 frameshift, 12 splice site, nine nonsense and seven promoter mutations, three large deletions, and two compound mutations with both missense and nonsense changes. Of these mutations, 36 were novel to the International Haemophilia B Mutation database (http://www.kcl.ac.uk/ip/petergreen/haemBdatabase.html). The Canadian F8 and F9 mutation database reflects the allelic heterogeneity of HA and HB, and is similar to previously described populations. This report represents the largest and longest duration experience of a national hemophilia genotyping program documented, to date.
authors.forename: Natalia
authors.initials: N
authors.lastname: Rydz
authors.affiliation: Medicine, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Rydz
authors.initials: R
authors.lastname: Natalia
authors.forename: Jayne
authors.initials: J
authors.lastname: Leggo
authors.forename: Leggo
authors.initials: L
authors.lastname: Jayne
authors.forename: Shawn
authors.initials: S
authors.lastname: Tinlin
authors.forename: Tinlin
authors.initials: T
authors.lastname: Shawn
authors.forename: Paula
authors.initials: P
authors.lastname: James
authors.forename: James
authors.initials: J
authors.lastname: Paula
authors.forename: David
authors.initials: D
authors.lastname: Lillicrap
authors.forename: Lillicrap
authors.initials: L
authors.lastname: David
mesh_terms: D002170:Canada / Q000453:epidemiology; D004252:DNA Mutational Analysis; D030541:Databases, Genetic; D005091:Exons / Q000235:genetics; D005164:Factor IX / Q000235:genetics*; D005169:Factor VIII / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D006580:Genetic Carrier Screening; D005820:Genetic Testing; D006467:Hemophilia A / Q000453:epidemiology / Q000235:genetics*; D002836:Hemophilia B / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D007438:Introns / Q000235:genetics; D008297:Male; D009154:Mutation; D010641:Phenotype; D011296:Prenatal Diagnosis; D022821:RNA Splice Sites; D012189:Retrospective Studies; D017422:Sequence Analysis, DNA; D057345:Sequence Inversion; D009626:Terminology as Topic; D056728:von Willebrand Disease, Type 2 / Q000453:epidemiology / Q000235:genetics
chemical_list: D022821:RNA Splice Sites; D005169:Factor VIII; D005164:Factor IX