Two novel and one recurrent missense mutation in the factor XIII A gene in two Dutch patients with factor XIII deficiency
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 het... Mehr ...
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Dokumenttyp: | Artikel |
Erscheinungsdatum: | 2001 |
Reihe/Periodikum: | British Journal of Haematology ; volume 112, issue 2, page 513-518 ; ISSN 0007-1048 1365-2141 |
Verlag/Hrsg.: |
Wiley
|
Schlagwörter: | Hematology |
Sprache: | Englisch |
Permalink: | https://search.fid-benelux.de/Record/base-26690556 |
Datenquelle: | BASE; Originalkatalog |
Powered By: | BASE |
Link(s) : | http://dx.doi.org/10.1046/j.1365-2141.2001.02577.x |
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.