Investigation on abnormal gene loci of a Chinese pedigree with hereditary combined deficiency of blood coagulation factor XI, XII, and protein S

In order to clarify the interaction mechanism, the phenotype and abnormal gene loci of FXI, FXII, and PS were investigated in this study.Chinese pedigree with hereditary combined deficiency of coagulation factor (F) XI, FXII, and PS was enrolled in our study. Activated partial thromboplastin time (APTT), partial thromboplastin time (PT), FXI:C, FXII:C, and protein S (PS):C were determined using the one-stage coagulation method. FXI:antigen (Ag), FXII:Ag, and PS:Ag were detected using enzyme-linked immunosorbent assay (ELISA). Exons and introns of the FXI, FXII, and PS genes were amplified by polymerase chain reaction (PCR), and gene sequencing results were analyzed using Chromas software.A deletion of two bases located in introns A-149 and-150 within the FXI gene of the proband, his father, wife, and both sons. A missense variant in exon 14 (GGT → AGT, Gly542Ser) within FXII of the proband, his parents, and both sons. Four variants in exon 4 within the PS gene of all members of the pedigree: GTT → GTG (Val46Val), CGC → CTC (Arg49Leu), CGT → CAT (Arg60His), and CAG → TAG (Gln61stop).None of the pedigree members showed a tendency for bleeding or thrombosis. Therefore, we speculated that the lack of coagulation factors counteracted the lack of PS, restoring the balance between the coagulation and anticoagulation systems. Another possible explanation is that these defects individually have only partial penetrance.