Two novel and one recurrent missense mutation in the factor XIII A gene in two Dutch patients with factor XIII deficiency.

Autor: Gómez García, E. B., Poort, S. R., Stibbe, J., Sturk, A., Schaap, M. C. L., Kappers, M., Bertina, R. M.
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Zdroj: British Journal of Haematology; Feb2001, Vol. 112 Issue 2, p513-518, 6p, 4 Charts
Abstrakt: 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. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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