Haematologica (Jun 2010)

Identification of eight novel coagulation factor XIII subunit A mutations: implied consequences for structure and function

  • Vytautas Ivaskevicius,
  • Arijit Biswas,
  • Carville Bevans,
  • Verena Schroeder,
  • Hans Peter Kohler,
  • Hannelore Rott,
  • Susan Halimeh,
  • Petro E. Petrides,
  • Harald Lenk,
  • Manuele Krause,
  • Bruno Miterski,
  • Ursula Harbrecht,
  • Johannes Oldenburg

DOI
https://doi.org/10.3324/haematol.2009.017210
Journal volume & issue
Vol. 95, no. 6

Abstract

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Background Severe hereditary coagulation factor XIII deficiency is a rare homozygous bleeding disorder affecting one person in every two million individuals. In contrast, heterozygous factor XIII deficiency is more common, but usually not associated with severe hemorrhage such as intracranial bleeding or hemarthrosis. In most cases, the disease is caused by F13A gene mutations. Causative mutations associated with the F13B gene are rarer.Design and Methods We analyzed ten index patients and three relatives for factor XIII activity using a photometric assay and sequenced their F13A and F13B genes. Additionally, structural analysis of the wild-type protein structure from a previously reported X-ray crystallographic model identified potential structural and functional effects of the missense mutations.Results All individuals except one were heterozygous for factor XIIIA mutations (average factor XIII activity 51%), while the remaining homozygous individual was found to have severe factor XIII deficiency (