Identification of a novel mutation combination in factor XIII deficiency: genetic update to the first reported case in the United States

International Journal of Hematology
Amy HalverstadtJames M Hagberg

Abstract

A 1967 report described the first known case of congenital factor XIII (FXIII) deficiency in the United States in a male patient with a severe hemorrhagic disorder. The patient's family presented no symptoms of the disorder, but the members were found to have half the normal FXIII activity. Although the molecular basis of the disorder could not be evaluated at the time, the results suggested an autosomal recessive inherited disorder. We sequenced all of the exons and the flanking regions in the genes for the FXIII A and B subunits of the patient, his family, and 18 unrelated individuals. We report the novel combination of an Arg-to-Cys mutation at codon 78 and a G-to-C mutation at the intron 5/exon 6 splice junction in the patient's FXIIIA gene. The missense-splice junction mutation combination appears to have caused the patient's FXIIIA deficiency, because the remaining family members, who present no symptoms and have no clinical diagnoses of FXIII deficiency, have one or the other of the 2 mutations but not both. Additionally, the 18 unrelated individuals are homozygous wild type at these loci. The molecular consequences of these mutations appear to be an abnormality in protein conformation or folding and/or a reduced product...Continue Reading

References

Jul 19, 1994·Proceedings of the National Academy of Sciences of the United States of America·V C YeeD C Teller
Jan 1, 1996·Seminars in Thrombosis and Hemostasis·V C YeeD C Teller
Jun 24, 1999·Thrombosis Research·L MuszbekZ Hevessy
Dec 3, 1999·British Journal of Haematology·R Anwar, K J Miloszewski
Nov 8, 2003·International Journal of Hematology·Baohua DuanZhenyi Wang
Dec 26, 2003·Human Mutation·Flora PeyvandiPier Mannuccio Mannucci
Jan 1, 2007·Biochemistry and Molecular Biology Education : a Bimonthly Publication of the International Union of Biochemistry and Molecular Biology·Judith G Voet, Donald Voet

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Citations

Aug 2, 2011·The American Journal of the Medical Sciences·Eva NourbakhshKenneth Nugent
Jun 7, 2011·Blood Reviews·Arijit BiswasJohannes Oldenburg

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