A novel frameshift mutation in exon 4 causing a deficiency of high-molecular-weight kininogen in a patient with splenic infarction

Intern Med. 2014;53(3):253-7. doi: 10.2169/internalmedicine.53.0737.

Abstract

High-molecular-weight kininogen (HMWK) deficiency is a very rare hereditary disorder. We herein report a case of HMWK deficiency with splenic infarction. The HMWK activity of the proband was markedly decreased (0.9%). Direct sequencing of his HMWK gene showed a homozygous "TC" insertion at c523-524 in exon 4. This insertion led to an amino acid substitution, Ser175Ser, resulting in a frameshift mutation and a premature stop codon in amino acid 183. Furthermore, the HMWK activity was also reduced in the patient's three children, who exhibited the heterozygous "TC" insertion at c523-524 in exon 4. This is the first report of this gene alteration in a patient with HMWK deficiency.

Publication types

  • Case Reports

MeSH terms

  • Aged
  • Blood Coagulation Disorders / complications
  • Blood Coagulation Disorders / diagnosis*
  • Blood Coagulation Disorders / genetics*
  • Exons / genetics*
  • Frameshift Mutation / genetics*
  • Humans
  • Kininogen, High-Molecular-Weight / deficiency*
  • Kininogen, High-Molecular-Weight / genetics
  • Male
  • Pedigree
  • Splenic Infarction / complications
  • Splenic Infarction / diagnosis*
  • Splenic Infarction / genetics*

Substances

  • Kininogen, High-Molecular-Weight

Supplementary concepts

  • Flaujeac factor deficiency