Compound Heterozygous Nonsense Mutations Leading to Hereditary Deficiency of Coagulation Factor XI in a Chinese Pedigree

The objective is to identify the gene mutations responsible for the deficiency of factor XI (FXI) in a Chinese pedigree. The FXI activity was tested with clotting assay. The F11 gene was amplified by PCR with direct sequencing. ClustalX-2.1-win and three online bioinformatics softwares were used to study the conservatism and harm of the mutation. The proband was a 70-year-old male and had a prolonged APTT of 67.8s. The corrected APTT was 28.3s and he had reduced FXI: activity of 0.8%. His son and daughter had normal APTT of 26s and 27.3s and FXI:C of 72% and 75%, respectively. DNA sequencing analysis showed the proband carried a compound heterozygous g.841C>T and g.1556G>A mutation , resulting in Ser281Stop and Trp519Stop, respectively, which caused premature termination of transcription in the F11. His son had the heterozygous g.841C>T mutation of F11 and his daughter had the heterozygous g.1556G>A mutation of F11. The three bioinformatics softwares indicated that the mutation had affected the function of the protein. The two nonsense mutations had been reported previously in different patient, but this is the first time to be reported in the proband, which was responsible for the decrease of FXI: activity.