title: Eighteen unrelated patients with factor XI deficiency, four novel mutations and a 100% detection rate by denaturing high-performance liquid chromatography.
abstract: Factor XI (FXI) deficiency is an autosomal bleeding disorder of variable severity. Inheritance is not completely recessive as heterozygotes may display a distinct, if mild, bleeding tendency. Eighteen unrelated FXI-deficient patients were screened blind by fluorescent single-stranded conformation polymorphism (F-SSCP) analysis and denaturing high-performance liquid chromatography (dHPLC). Mutations were detected in 14 of the 18 patients ( approximately 78%) by F-SSCP and in all 18 patients by dHPLC. Dideoxy sequencing confirmed the mutations in all 18 patients: eight of the mutations being novel (four of which were in previously reported patients). This showed dHPLC to be a highly sensitive, reliable technique for mutation screening in heterogeneous disorders.
authors.affiliation: Haemophilia Reference Centre, Centre for Haemostasis and Thrombosis, St. Thomas' Hospital, London, UK. Mike.Mitchell@gstt.sthames.nhs.uk
authors.forename: Michael
authors.initials: M
authors.lastname: Mitchell
authors.forename: Purvee
authors.initials: P
authors.lastname: Harrington
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Cutler
authors.forename: Savita
authors.initials: S
authors.lastname: Rangarajan
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Savidge
authors.forename: Anwar
authors.initials: A
authors.lastname: Alhaq
mesh_terms: D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004252:DNA Mutational Analysis; D005173:Factor XI Deficiency / Q000175:diagnosis* / Q000235:genetics*; D006801:Humans; D007585:Jews; D009154:Mutation; D018807:Polymorphism, Single-Stranded Conformational