Abstract
Coagulation factor XIII (FXIII) deficiency is a rare recessive bleeding
disorder. Severe patients are caused by a complete absence of FXIIIA
protein in plasma, but researches on the molecular mechanisms are
limited. This study was to analyze the pathogenic mechanisms of three
congenital FXIII deficiency patients. Plasma FXIII activities and
antigens were significantly decreased in patients compared to healthy
controls by fluorescent assay and western blot. One frameshift mutation
and four missense mutations (p.Trp188Cys, p.His374Arg, p.Thr559Pro and
p.His717Arg) around the catalytic core were identified. The mRNA levels
of four mutants were nearly normal in COS7 cells, and the FXIIIA protein
could be detected in cell lysis but not be expressed in the supernatant.
Confocal microscopy studies showed clear outlines of cells with both
wild FXIII and mutants, but some mutants gathered into clusters neither
in the endoplasmic reticulum nor in the Golgi apparatus of cytoplasm,
compared to the diffusely-distributed wild FXIII. Considering the above,
we concluded that the three cases of FXIII deficiency were caused by
p.Trp188Cys, p.His374Arg, p.Thr559Pro and p.His717Arg mutations in
FXIIIA gene, which led to the gathering of FXIIIA in cytoplasm and then
blocking its transportation into medium.