A Novel Phenotype of the Factor 5 Gene Mutation (Homozygote Met1736Val and Heterozygote Asp68His) Is Associated With Moderate Factor V Deficiency

Abstract

BackgroundFactor V (FV) deficiency is a rare disease, with a low incidence rate in Asia. Therefore, the F5 mutation in the Taiwanese population is poorly understood.MethodsA Chinese family with FV deficiency was included, and the patient and his family members underwent mutation analysis. Then, patients from Keelung City (Taiwan) were screened for F5 polymorphism; the Chang Gung Human Database was used to determine single-nucleotide variants in the non-FV-deficient patient population.ResultsEight mutation sites on the F5 gene locus, including exon 16 homozygote Met1736Val and seven heterozygous mutations, including Asp68His, were found. Moreover, Met1736Val was found to be the dominant mutation in people living in the Taiwan community, and this result was compared with the records of the Chang Gung Human Database. The above-mentioned polymorphisms may result in a variable incidence of FV deficiency in Keelung City, thereby facilitating carrier diagnosis and prenatal diagnosis in most FV-deficient families.ConclusionThe homozygote Met1736Val and the co-inheritance of the Asp68His F5 gene are unique and worthy of screening in FV-deficient patients.

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 ].…”

“…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 ], and not in Western regions. Hence, these two genetic variants may be specific to East-Asian populations.…”

“…According to the Report on the Annual Global Survey 2020 published by the World Federation of Hemophilia [13], 2554 FVD cases have been identified worldwide. However, only a few cases were reported in Taiwan [14][15][16][17][18]. In this study, we characterized the clinical and laboratory features of seven unrelated index patients with FVD in Taiwan.…”