title: A novel F11 mutation in a Korean pediatric patient with recurrent epistaxis.
abstract: Congenital FXI deficiency (hemophilia C) is a rare bleeding disorder that has been documented mostly in Ashkenazi Jews. Unlike other hemophilias, bleeding tendency varies considerably among individuals, and FXI deficiency rarely manifests as spontaneous bleeding. FXI deficiency is caused primarily by mutations in the F11 gene. Herein, we report a case of a 10-year-old boy with recurrent nose bleeding due to FXI deficiency who was confirmed to have a novel mutation in F11. A molecular analysis of DNA extracted from peripheral blood collected from the patient [FXI clotting activity (FXI:C): 11%] revealed compound heterozygous mutations, Q226X and L424F, in F11, consistent with the severe disease phenotype of the patient. Pedigree analysis showed that the patient received L424F from his father (FXI:C = 49%) and Q226X from the mother (FXI:C = 48%). The sister (FXI:C = 47%) of the patient only had L424F, presumably inherited from her father. Multiple sequence alignment demonstrated that L424 is highly conserved across mammals, indicating that it is important for the function of FXI. In-silico analysis indicated that replacement of L424 by phenylalanine had a detrimental influence on FXI, consistent with the severe phenotype of the patient. Compilation of FXI deficiency cases in east Asian populations would be of great value because different populations appear to have different F11 mutation spectra.
authors.affiliation: Department of Laboratory Medicine, Yonsei University Wonju College of Medicine, Seoul, Korea.
authors.forename: Juwon
authors.initials: J
authors.lastname: Kim
authors.forename: Yoonjung
authors.initials: Y
authors.lastname: Kim
authors.forename: Seam
authors.initials: S
authors.lastname: Shin
authors.forename: Chuhl Joo
authors.initials: CJ
authors.lastname: Lyu
authors.forename: Jong Rak
authors.initials: JR
authors.lastname: Choi
authors.forename: Kyung-A
authors.initials: KA
authors.lastname: Lee
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D044466:Asian People; D001483:Base Sequence; D002648:Child; D004844:Epistaxis / Q000150:complications / Q000235:genetics*; D005172:Factor XI / Q000235:genetics*; D005173:Factor XI Deficiency / Q000150:complications / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D007930:Leucine / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D010649:Phenylalanine / Q000235:genetics; D012008:Recurrence; D016415:Sequence Alignment
chemical_list: D010649:Phenylalanine; D005172:Factor XI; D007930:Leucine