Factor V deficiency caused by a novel nonsense mutation (Gln2031stop) in a Chinese patient

Abstract

Congenital factor V deficiency is a rare bleeding disorder characterized by low coagulant activity, associated with variable phenotypic expression. Among rare inherited coagulopathies, the molecular basis of factor V deficiency is rarely described because of its relatively low prevalence in the general population. Recently, we detected two genetic variations in factor V of a Chinese patient with hereditary factor V deficiency. One was a heterozygous nonsense mutation, C67868T in exon 22, which resulted in Gln2031stop substitution in the C1 domain of factor V. The other was a previously described polymorphism, G1618A in exon10, leading to Arg485Lys substitution. We deduced that the nonsense mutation is responsible for the factor V deficiency, whereas the Arg485Lys polymorphism is expected to compensate for the low plasma factor V levels. Of note, the nonsense mutation has been confirmed to be a novel mutation.

A novel homozygous missense mutation (Met527Ile) in a consanguineous marriage family with inherited factor XII deficiency

“…It is interesting that none of the mutant members had a history of bleeding or thrombotic episodes. Subjects with a deficiency in FXII were asymptomatic and do not undergo spontaneous or injury-related bleeding, which was quite distinct from the other coagulation factor deficiency [14,15]. The relation between FXII deficiency and thrombotic events was controversial.…”

Significance of the p.Phe218Ser and p.Gly304Glu F5 Variants in Hereditary Factor V Deficiency

“…Peripheral blood from all participants was collected into anticoagulated vacutainer tubes with sodium citrate, and genomic DNA was extracted from peripheral blood using DNA blood extraction kits (Tiangen Biotech, Beijing, China). Thirty-one pairs of primers were designed to cover all exons and their flanking regions of the F5 , as previously described [10]. Subsequently, the primers were synthesized by the Shanghai Sunny Biotechnology Corporation (Shanghai, China).…”

Congenital factor V deficiency in Taiwan: identification of a novel variant p.Tyr1813∗ and two variants specific to East Asians

“…Because of the large size of F5 and lack of mutational hotspots, most FVD-causing mutations are considered as unique and segregated to a specific family or region. To our knowledge, p.Asp96His has been reported only in Taiwan [15,16,18], China [28,29], and Korea [30], whereas p. Gly420Cys has been identified in Taiwan [14], China [31,32], Japan [33] Seven of the genetic variants associated with FVD identified in our study have been previously described in the literature, including p.Asp2222Gly [18,24,25], p.Asp96His [15,16,18], p.Gly420Cys [14,[31][32][33], p.His175Arg [15], p. Tyr558Ser [34], p.Gln2059 Ã [35], and p.Arg2102Cys [15,36]. We previously reported the functional and molecular characteristics of the variants p.Asp96His [16] and p. His175Arg [15].…”

“…Seven of the genetic variants associated with FVD identified in our study have been previously described in the literature, including p.Asp2222Gly [ 18 , 24 , 25 ], p.Asp96His [ 15 , 16 , 18 ], p.Gly420Cys [ 14 , 31 – 33 ], p.His175Arg [ 15 ], p.Tyr558Ser [ 34 ], p.Gln2059∗ [ 35 ], and p.Arg2102Cys [ 15 , 36 ]. We previously reported the functional and molecular characteristics of the variants p.Asp96His [ 16 ] and p.His175Arg [ 15 ].…”