Novel deleterious mutation in the F12 gene in a Korean family with severe coagulation factor XII deficiency

Blood Coagul Fibrinolysis. 2010 Oct;21(7):683-6. doi: 10.1097/MBC.0b013e32833e429c.

Abstract

Coagulation factor XII (FXII) is involved in the initiation of blood coagulation, fibrinolysis, complement systems, and bradykinin generation. Hereditary deficiency of FXII is caused by mutations in the F12 gene. In this report, we describe a Korean family with severe FXII deficiency from F12 mutations. The proband was a 46-year-old woman and was shown to have a markedly prolonged activated partial thromboplastin time at 126.7 s (reference range, 29-42 s) on routine health checkup. She had no history of bleeding tendency. Complete correction of prolonged activated partial thromboplastin time on mixing test prompted us to perform factor assays, which revealed a markedly decreased FXII activity (<0.5%; below the detection limit). Direct sequencing analyses for F12 showed that the proband was compound heterozygous for two deleterious mutations, c.249delG (p.Q83HfsX12) and c.405C>A (p.C135X). Family study showed that her sister with prolonged activated partial thromboplastin time at 83.8 s and FXII activity less than 0.5% was also compound heterozygous for the mutations. Q83HfsX12 was a novel frameshift mutation in exon 4 of F12, and C135X is a nonsense mutation previously reported in a Korean patient who was homozygous for the mutation. Thus, the C135X mutation is a recurrent mutation in Korean individuals with FXII deficiency, potentially with a founder effect.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Codon, Nonsense
  • DNA Mutational Analysis
  • Factor XII / genetics*
  • Factor XII Deficiency / genetics*
  • Family
  • Female
  • Founder Effect
  • Frameshift Mutation
  • Heterozygote
  • Humans
  • Korea
  • Middle Aged
  • Mutation*
  • Partial Thromboplastin Time
  • Point Mutation
  • Sequence Deletion
  • Siblings

Substances

  • Codon, Nonsense
  • Factor XII