Molecular mechanism analysis of a family with hereditary coagulation FXI deficiency caused by compound heterozygous mutations.

OBJECTIVE

The purpose of this study was to determine the molecular basis of a Chinese family with factor XI (FXI) deficiency.

METHODS

The qRT-PCR was used to detect the transcription of F11 mRNA in transfected cells. ELISAs and western blot were used to detect the expression of FXI protein in culture media and lysates.

RESULTS

Genetic analysis revealed that the proband carried a heterozygous nonsense mutation c.1107C>A (p.Tyr351stop) in exon 10 and a heterozygous missense mutation c.1562A>G (p.Tyr503Cys) in exon 13. The expression study revealed that p.Tyr351stop mutation resulted in the degradation of F11 mRNA. The p.Tyr503Cys mutation, however, had no effects on biosynthesis and secretion of FXI protein, but it had affected the catalytic activity of FXI.

CONCLUSION

The inherited FXI deficiency of this family is related to nonsense mutation p.Tyr351stop and missense mutation p.Tyr503Cys.