Premium
Two novel and one recurrent missense mutation in the factor XIII A gene in two Dutch patients with factor XIII deficiency
Author(s) -
Gómez García E. B.,
Poort S. R.,
Stibbe J.,
Sturk A.,
Schaap M. C. L.,
Kappers M.,
Bertina R. M.
Publication year - 2001
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.2001.02577.x
Subject(s) - transversion , proband , missense mutation , factor xiii deficiency , exon , compound heterozygosity , factor xiii , mutation , protein subunit , genetics , microbiology and biotechnology , allele , biology , antigen , gene , endocrinology , chemistry , immunology , fibrin
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.