Genetic analysis of a pedigree with combined factor XII and factor XI deficiency

The objective of the present study was to identify the gene mutations of factor XI (FXI) and factor XII (FXII) in a Chinese pedigree with combined congenital FXI and FXII deficiencies. The proband was a 40-year-old woman with deficiency in both FXI (49%) and FXII (0%) activities. Blood samples from 10 other members of her family were collected and used for detection of FXI, FXII activities (FXI: C, FXII: C) and antigen levels. Genetic analysis to detect mutations in FXI, FXII genes was also performed. The proband's mother, three brothers, two sisters, her son and her daughter all have lowered FXII: C. Furthermore, her mother and one of her brothers also have lowered FXI: C. Gene sequencing for FXI in affected members revealed a heterozygous C23179T point mutation in exon 11 resulting in substitution of arginine 396 by cysteine. Gene sequencing for FXII revealed a C46T in the promoter region and a deletion mutation of two nucleotides CA at position 9160 and 9161 in exon 5. The deletion mutation can lead to frameshift mutation and premature termination of transcription in exon 6. We found a new heterozygous missense mutation in the FXI gene and a new nonsense mutation of two nucleotides deletion which caused frameshift mutation and premature termination of transcription in the FXII gene in a Chinese family with combined FXI and FXII deficiencies.