title: Two novel and one recurrent missense mutation in the factor XIII A gene in two Dutch patients with factor XIII deficiency.
abstract: Congenital factor XIII (FXIII) deficiency is a rare autosomal recessive disorder, usually attributed to a defect in the FXIII A subunit, whose genetic basis has been studied in a number of cases. We describe here the genetic variations found in two unrelated patients with FXIII deficiency. Both patients, under prophylactic substitution with FXIII concentrate, showed low plasma FXIII A subunit antigen levels with undetectable A subunit antigen in the platelets and normal plasma B antigen levels, which indicate that the defects are present in the A subunit of the molecule. Both probands were heterozygous for a previously reported G-->A transversion in exon 8 of the FXIII A subunit gene (Arg326Gln substitution). Proband 1 was also heterozygous for a novel G-->T transversion in exon 7, which predicts a Val316Phe substitution. Two of her sons were heterozygous for this mutation and showed low FXIII activity and FXIII A subunit antigen levels. Val316 is a well-conserved amino acid among the transglutaminase family, located within the core domain, close to the Cys314 member of the catalytic triad. Proband 2 had a unique 2-bp (TT) insertion in one of the alleles within or adjacent to the -7 to -20 T tail of intron A. This insertion was not found in 50 healthy individuals, which supports this being the second mutation in this patient.
authors.affiliation: Department of Haematology, University Hospital Dijkzigt, Rotterdam, The Netherlands. gomezgarcia@haed.azr.nl
authors.forename: E B
authors.initials: EB
authors.lastname: Gómez García
authors.forename: S R
authors.initials: SR
authors.lastname: Poort
authors.forename: J
authors.initials: J
authors.lastname: Stibbe
authors.forename: A
authors.initials: A
authors.lastname: Sturk
authors.forename: M C
authors.initials: MC
authors.lastname: Schaap
authors.forename: M
authors.initials: M
authors.lastname: Kappers
authors.forename: R M
authors.initials: RM
authors.lastname: Bertina
mesh_terms: D000328:Adult; D000818:Animals; D001324:Autoantigens / Q000097:blood; D001483:Base Sequence; D002648:Child; D017931:DNA Primers; D005176:Factor XIII / Q000235:genetics* / Q000276:immunology; D005177:Factor XIII Deficiency / Q000235:genetics* / Q000276:immunology; D005260:Female; D006801:Humans; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D009426:Netherlands; D017354:Point Mutation; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA
chemical_list: D001324:Autoantigens; D017931:DNA Primers; D005176:Factor XIII; C054380:factor XIIIb