title: Sequencing of the factor 8(F8) coding regions in 10 Turkish hemophilia A patients reveals three novel pathological mutations, and one rediagnosis of von Willebrand's disease type 2N.
abstract: The most common cause for severe cases of hemophilia A is the homologous recombination involving intron 22 and related sequences outside the F8 gene. F8 coding regions of the gene including the exon/intron junctions were sequenced in 10 Turkish hemophilia A patients all of whom have been typed negative for intron 22 inversion and who did not have a detectable change by DGGE analysis. Pathological changes including two novel deletions (c. 205del CT and c. 3699del ACAT), one novel missense mutation (9546A) and two recurrent missense mutations were observed in five patients. The c. 2110C > T is another novel pathological change affecting exonic splicing enhancer site in two patients. One of the remaining three patients had a recurrent vWD type 2N mutation in the F8 binding site of the vWF (C788R). The S1269S polymorphism (c. 3864A > C) detected phenotype. Conclusively, sequencing of the promoter and the coding regions of 10 hemophilia A patients contributes four novel pathological mutations to the F8 mutations list and reveals a rediagnosis of hemophilia A but is still not sufficient to confirm hemophilia A phenotype in two patients.
authors.affiliation: Department of Molecular Biology and Genetics, Bogazici University, Istanbul, Turkey.
authors.forename: E
authors.initials: E
authors.lastname: Berber
authors.forename: I D
authors.initials: ID
authors.lastname: Fidanci
authors.forename: C
authors.initials: C
authors.lastname: Un
authors.forename: O
authors.initials: O
authors.lastname: El-Maarri
authors.forename: G
authors.initials: G
authors.lastname: Aktuglu
authors.forename: A
authors.initials: A
authors.lastname: Gurgey
authors.forename: T
authors.initials: T
authors.lastname: Celkan
authors.forename: A
authors.initials: A
authors.lastname: Meral
authors.forename: J
authors.initials: J
authors.lastname: Oldenburg
authors.forename: J
authors.initials: J
authors.lastname: Graw
authors.forename: N
authors.initials: N
authors.lastname: Akar
authors.forename: H
authors.initials: H
authors.lastname: Caglayan
mesh_terms: D004252:DNA Mutational Analysis; D003937:Diagnosis, Differential; D005169:Factor VIII / Q000235:genetics*; D006467:Hemophilia A / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D007438:Introns / Q000235:genetics; D008297:Male; D009154:Mutation; D011110:Polymorphism, Genetic; D014842:von Willebrand Diseases / Q000175:diagnosis*
chemical_list: D005169:Factor VIII