Inherited
factor XIII (FXIII) deficiency is known as one of the most rare
blood coagulation disorder in humans. In the present study, phenotype and genotype of eight FXIII deficient Polish patients from five unrelated families were compared. The patients presented with a severe phenotype demonstrated by a high incidence of intracerebral haemorrhages (seven of eight patients), haemarthrosis (six patients) and
bleeding due to
trauma (five patients). Introduction of regular substitution with FXIII concentrate prevented spontaneous
bleeding in seven patients. In all patients, mutations within the F13A gene have been identified revealing four missense mutations (Arg77Cys, Arg260Cys, Ala378Pro, Gly420Ser), one
nonsense mutation (Arg661X), one splice site mutation (IVS5-1 G>A) and one small deletion (c.499-512del). One homozygous large deletion involving exon 15 was detected by failure of PCR product. The corresponding mutations resulted in severely reduced FXIII activity and FXIII A-subunit
antigen concentration, while FXIII B-subunit
antigen remained normal or mildly decreased. Structural analysis demonstrated that the novel Ala378Pro mutation may cause a disruption of the FXIII catalytic triad leading to a non-functional
protein which presumably undergoes premature degradation. In conclusion, the severe phenotype with high incidence of intracranial
bleeding and haemarthrosis was in accordance with laboratory findings on FXIII and with severe molecular defects of the F13A gene.