title: Molecular genetic analysis of Korean patients with coagulation factor XII deficiency.
abstract: Coagulation factor XII (FXII) participates in the initiation of blood coagulation, fibrinolysis, complement systems, and bradykinin generation. Hereditary FXII deficiency is caused by mutations in the F12 gene. In this report, we describe three Korean patients with FXII deficiency. In all three patients, prolonged activated partial thromboplastin time (aPTT) was detected on preoperative coagulation screening, without a history of bleeding tendency. Patient 1 was a 4-year-old girl with congenital heart anomaly. Her aPTT was prolonged at 67.5 s (reference range, 29-42 s) and the FXII activity was 5% (48-177%). Patient 2 was a 50-year-old man with anal fistula. His aPTT was 95.2 s and FXII activity was less than 0.5% (below the detection limit). Patient 3 was a 53-year-old woman with pituitary macroadenoma. Her aPTT was 238.8 s and FXII activity was less than 0.5%. Direct sequencing analyses of F12 revealed two mutations in all three patients. Patient 1 was compound heterozygous for two missense mutations, c.1583C>T (p.S528F) and c.1744G>A (p.G582S). Patient 2 was homozygous for a nonsense mutation, c.405C>A (p.C135X). Patient 3 was compound heterozygous for a frameshift mutation and a missense mutation, c.1093_1094insC (p.K365QfsX69) and c.1744G>A (p.G582S). All four mutations were novel. To the best of our knowledge, these are the first genetically confirmed cases of FXII deficiency in Korea. FXII deficiency should be included in differential diagnoses of prolonged aPTT, particularly in those without bleeding tendency.
authors.affiliation: Department of Laboratory Medicine & Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Korea.
authors.forename: Min-Jung
authors.initials: MJ
authors.lastname: Kwon
authors.forename: Hee-Jin
authors.initials: HJ
authors.lastname: Kim
authors.forename: Ki-O
authors.initials: KO
authors.lastname: Lee
authors.forename: Chul Won
authors.initials: CW
authors.lastname: Jung
authors.forename: Sun-Hee
authors.initials: SH
authors.lastname: Kim
mesh_terms: D044466:Asian People / Q000235:genetics*; D002675:Child, Preschool; D018389:Codon, Nonsense; D005174:Factor XII / Q000235:genetics*; D005175:Factor XII Deficiency / Q000235:genetics*; D005260:Female; D016368:Frameshift Mutation; D006801:Humans; D007723:Korea; D008297:Male; D008875:Middle Aged; D009154:Mutation; D020125:Mutation, Missense; D010314:Partial Thromboplastin Time
chemical_list: D018389:Codon, Nonsense; D005174:Factor XII