Publication: Identification of a new mutation (Gly420Ser), distal to the active site, that leads to factor XIII deficiency
1
Issued Date
2000-10-21
Resource Type
ISSN
09024441
Other identifier(s)
2-s2.0-0033819617
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Mahidol University
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SCOPUS
Bibliographic Citation
European Journal of Haematology. Vol.65, No.4 (2000), 279-284
Suggested Citation
Sasichai Kangsadalampai, Pa Thai Yenchitsomanus, Gareth Chelvanayagam, Nunghathai Sawasdee, Vichai Laosombat, Philip Board Identification of a new mutation (Gly420Ser), distal to the active site, that leads to factor XIII deficiency. European Journal of Haematology. Vol.65, No.4 (2000), 279-284. doi:10.1034/j.1600-0609.2000.065004279.x Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/26152
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Title
Identification of a new mutation (Gly420Ser), distal to the active site, that leads to factor XIII deficiency
Abstract
The molecular defects of the factor XIII A subunit gene were studied in a patient with factor XIII deficiency. Mutation analysis was performed on amplified DNA from each exon of this gene by single-strand conformation polymorphism (SSCP) and DNA sequencing techniques. A substitution of guanine by adenine at nucleotide 1258 in exon 10 of the coagulation factor XIII A subunit gene has been identified in the patient. The mutation results in the replacement of Gly420 by Ser in the core domain of the enzyme. Restriction enzyme analysis of amplified exon 10 DNA confirmed that the patient was homozygous for this mutation. A family study revealed that the mutation was inherited from both parents, who were first cousins. The potential effects of the mutation were predicted by molecular modeling of the amino acid substitution within the coordinates of the crystal structure. The substitution occurred within the core domain of the enzyme at a residue completely conserved among all known members of the transglutaminase family. The model of the mutant protein suggests that although the substitution of Gly420 by Ser causes only minor readjustment of the residues and does not appear to be particularly deleterious in terms of structure, the mutation is, however, likely to decrease the molecule's ability to undergo the conformational change that is thought to be required for full transglutaminase activity. Our data strongly support the previously published information about the functional significance of the residues surrounding, but not forming, the catalytic pocket in the A subunit of factor XIII.