Abstract
The knowledge of the molecular basis of factor XIII deficiency has improved significantly
in recent years. Almost 20 different mutations have been described in the gene coding
for the factor A-subunit and 3 mutations in the gene coding for the B-subunit. Half
of the mutations in the factor XIIIa A-subunit gene are nonsense mutations that result
in premature termination of translation. Three of them are frameshift mutations that
are caused by minor deletions. Two of them are splicing mutations and 3 are stop mutations
that are caused by single nucleotide substitutions. Ten of the mutations are missense
mutations caused by nucleotide transitions leading to amino acid substitutions. In
the factor XIII B-subunit gene, the 3 mutations are an amino acid substitution, a
splicing mutation, and a trinucleotide insertion. These mutations explain the disease
in the two families reported to have XIII B-subunit deficiency. In factor XIII A-subunit
deficiency, the genetic defects have been characterized so far only in a minority
of cases. In most of the reports of factor XIII A-subunit mutations, each family carries
its own mutation/mutations. However, in some populations such as Finns and Arabs some
enrichment of specific mutations has occured. Some international migration of a few
mutations has also been noted. The structural and functional effects of the mutations
have been analyzed by studying the expression of the factor XIII subunits on mRNA
and protein levels in vivo or in vitro, and by utilizing the threedimensional model
of crystallized factor XIII A-subunit in modeling of the missense mutations.
Key words:
Factor XIII A-subunit - factor XIII B-subunit - gene mutations - factor XIII deficiencies
- fibrin crosslinking
