Novel Y283C mutation of the A subunit for coagulation factor XIII: molecular modelling predicts its impaired protein...

In an Italian patient with severe factor XIII deficiency, a novel mutation, Y283C (TAT to TGT), was identified heterozygously by nucleotide sequencing analysis in exon VII of the gene for the A subunit. The presence of this mutation was confirmed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis in the proband and his brother. Molecular modelling predicts that the mutant molecule would be misfolded. It is probable that the impaired folding of the mutant Y283C A subunit led to its instability, which is at least in part responsible for the factor XIII deficiency of this patient.