2007 Mutations in patients with factor V deficiency

Mutations in patients with factor V deficiency

Mutation (Name)	Location	Domain	Type	genotype	Origin	Activity U/dL	Antigen U/dL	Expression	comments	Reference
nt434 del G	Exon 4	A1	Frameshift	Het		45			Also FVII deficiency	1
Glu119stop	Exon 4	A1	Nonsense	Het		47				2
nt 585 del A Undefined	Exon 4	A1	Frameshift	Comp het	China	1	2			3
Ala221Val Undefined	Exon 6	A1	Missense	Comp het		29	39	Yes		4, 5
Ser234Trp Gene deletion	Exon 6	A1	Missense Deletion	Comp het		9			Chromosome 1q deletion	6
Lys310stop ( Amersfoort)	Exon 7	A1	Nonsense	Het	Netherlands	34	51			7
nt 1041 del 8 bp ( Seoul I) Tyr1702Cys* ( Seoul 2)	Exon 7 Exon 15	A1 A3	Frameshift Missense	Comp het	South Korea	1	3			7
Gly392Cys* nt 4798 del G	Exon 8 Exon 14	A2 A3	Missense Splicing	Comp het	China	<1	1			8
Gly392Cys*	Exon 8	A2	Missense	Hom	Taiwan	1.7	2.5	Yes		9
IVS8- 2A>G	Intron 8		Splicing	Hom	China					10
Ile417Thr (Ogden) nt4699 ins 4 bp*	Exon 9 Exon 13	A2 B	Missense Frameshift	Comp het		<5	<5			11
Cys472Gly nt 5038 ins A	Exon 10 Exon 15	A2 A3	Missense Frameshift	Comp het	UK	<1	2	Yes		12
nt 1599 del G	Exon 10	A2	Frameshift	Hom	South Asia	<1	4			13
Arg506stop	Exon 10	A2	Nonsense	Het		33				14
nt 1611 G>T	Exon 10	A2	Splicing	Hom		<1	8			15
Tyr530Ser*	Exon 11	A2	Missense		China					16
Tyr530Ser* IVS16-1 G>T	Exon 11 Intron 16	A2	Missense Splicing	Comp het	China					17
Cys585Arg (Nijkerk)	Exon 12	A2	Missense	Het	Netherlands	52	64			7
nt 1853 ins C Y1702C*	Exon 12 Exon 15	A2 A3	Frameshift Missense	Comp het	Japan	<3	<1	Yes Yes		18
nt 2148 del AG Gly 2079Val	Exon 13 Exon 23	B C2	Frameshift Missense	Comp het	China	0.1	1.5			10, 19
Arg712stop*	Exon 13	B	Nonsense	Het					Trans with FV Leiden	20
Arg712stop* Val1813Met	Exon 13 Exon 17	B A3	Nonsense Missense	Comp het	UK	<1	5	Yes		12
Gln773stop ( Casablanca)	Exon 13	B	Nonsense	Hom	Morocco	1	3			7, 21
nt 2572 del AA or AG	Exon 13	B	Frameshift	Hom	India		2.4			22
nt 2743 del AC	Exon 13	B	Frameshift	Hom		<1	<1			23
nt 2862 del T nt 5403 ins G ( Debrecen),	Exon 13 Exon 16	B A3	Frameshift Frameshift	Comp het		<1	1			24
Arg1002stop*	Exon 13	B	Nonsense	Hom	Puerto Rica	<1	<1			13
Arg1002stop* nt 6032 ins 5bp	Exon 13 Exon 21	B C1	Nonsense Frameshift	Comp het	South India	<1	<1			12
nt3296 del A	Exon 13	B	Frameshift	Hom	India		2.9			22
nt3471 del 4 bp	Exon 13	B	Frameshift	Hom	African American	<1				13
Arg1133stop*	Exon 13	B	Nonsense	Hom	Italy	<1	<1		Cis with FV Leiden	25
nt 3616 ins TC	Exon 13	B	Frameshift	Het		42	54		Trans with FV Leiden	26, 27, 28
nt 3799 del C	Exon 13	B	Frameshift	Hom	India		<1			22
nt 3924 del 4 bp	Exon 13	B	Frameshift	Hom		2	<1			29
nt 4204 del C ( Utrecht)	Exon 13	B	Frameshift	Hom	Turkey	<1	3			7
nt 4699 ins 4 bp* (Stanford)	Exon 13	B	Frameshift	Het		56			Trans with FV Leiden	30
nt 4699 ins 4 bp* (Stanford)	Exon 13	B	Frameshift	Het		44				30
Arg1606stop Tyr1702Cys*	Exon 14 Exon 15	A3 A3	Nonsense Missense	Comp het	Italy	<1	<1			12
Glu1608Lys*	Exon 14	A3	Missense	Het		56	51		Trans with FV Leiden	28, 31
Glu1608Lys*	Exon 14	A3	Missense	Het		38	50			31
Tyr1702Cys*	Exon 15	A3	Missense	Het	Italy	50	50		Trans with FV Leiden	32
Tyr1702Cys*	Exon 15	A3	Missense	Hom	Italy	1				32, 33
Tyr1702Cys* Undefined	Exon 15	A3	Missense	Comp het	Italy	<1				33
Tyr1702Cys*	Exon 15	A3	Missense	Hom	Slovenia	<1	<1			12
nt 5419 G>A	Exon 16	A3	Splicing	Het		72	73		Trans with FV Leiden	34
nt 5593 del T	Exon 17	A3	Frameshift	Het		50	48		Cis with FV Leiden	35
Gly1852Val	Exon 18	A3	Missense	Hom						36
Trp1854stop	Exon 18	A3	Nonsense	Hom	Turkey	2	1			12
Gln1894stop	Exon 19	C1	Nonsense	Het		62	46		Trans with FV Leiden	28
IVS19+3 A>T	Intron 19	C1	Splicing	Hom	Iran	<1	<1	Yes		37
Gly2032Asp	Exon 22	C1	Missense	Het	Italy	65	53	Yes	Cis with FV Leiden	38
nt 6212 del G	Exon 23	C1	Frameshift	Het		56	60		Trans with FV Leiden	28
Pro2070Leu	Exon 23	C2	Missense	Hom	Norway				The first patient described (Mary)	39
Arg2074Cys*	Exon 23	C2	Missense	Hom	Italy	4	2	Yes		40, 41
Arg2074His*	Exon 23	C2	Missense	Hom	Tunis	2	3			42
Gly2112Asp	Exon 24	C2	Missense	Het		59	52		Trans with FV Leiden	28
nt 6491 del 21 bp and nt 6523 del G	Exon 24	C2	Frameshift	Het		45	40		Trans with FV Leiden	35

Nucleotide numbers are based on the genebank file M16967 using the A of the ATG initiator methionine as +1
*A Mutation that was identified in more than 1 family

References

Traynis I, Jones CD, Gibb CB, Acharya SS, Zehnder JL: First molecular characterization of a patient with combined factor V and factor VII deficiency. Thromb Haemost 95:1031, 2006.
Mumford AD, McVey JH, Morse CV, et al: Factor V I359T: A novel mutation associated with thrombosis and resistance to activated protein C. Br J Haematol 123:496, 2003.
Hou LH, Xie F, Liu XE, et al: A novel mutation causes congenital factor V deficiency.Zhonghua Xue Ye Xue Za Zhi24:455, 2003.
Murray JM, Rand MD, Egan JO, et al: Factor V New Brunswick: Ala 221-to-Val substitution results in reduced cofactor activity.Blood86:1820, 1995.
Steen M, Miteva M, Villoutreix BO, et al: Factor V New Brunswick: Ala221Val associated with FV deficiency reproduced in vitro and functionally characterized.Blood102, 1316, 2003.
Caudill JS, Sood R, Zehnder JL, Pruthi RK, Steensma DP: Severe coagulation factor V deficiency associated with an interstitial deletion of chromosome 1Q. J Thromb Haemost, in press, 2007.
Van Wijk R, Nieuwenhuis K, van den Berg M, et al: Five novel mutations in the gene for human blood coagulation factor V associated with type I factor V deficiency.Blood98:358, 2001.
Fu Q, Wu W, Ding Q, et al: Type I coagulation factor V deficiency caused by compound heterozygous mutation of F5 gene.Haemophilia9:646, 2003.
Chen TY, Lin TM, Chen HY, et al: Gly392Cys missense mutation in the A2 domain of factor V causing severe factor V deficiency: molecular characterization by expression of the recombinant protein. Thromb Haemost 93:614, 2005
Fu QH, Zhou RF, Liu LG, et al: Identification of three F5 gene mutations associated with inherited coagulation factor V deficiency in two Chinese pedigrees.Haemophilia10:264, 2004.
Kling SJ, Griffee M, Flanders MM, Rodgers GM: Factor V deficiency caused by a novel missense mutation, Ile417Thr, in the A2 domain. J Thromb Haemost 4:481, 2006.
Montefusco MC, Duga S, Asselta R, et al: Clinical and molecular characterization of 6 patients affected by severe deficiency of coagulation factor V: Broadening of the mutational spectrum of factor V gene and in vitro analysis of the newly identified missense mutations.Blood 102:3210, 2003.
Schrijver I, Hong DW, Mandle L, et al: High frequency of premature termination mutations in the factor V gene: three factor V deficiency case reports and a mutation review. Thromb Haemost 93:610, 2005.
Mirochnik O, Halim-Kertanegara N, Henniker AJ, et al: A novel factor V null mutation at Arg 506 causes a false positive factor V Leiden result.Thromb Haemost82:1198, 1999.
Schrijver I, Koerper MA, Jones CD, Zehnder JL: Homozygous factor V splice site mutation associated with severe factor V deficiency.Blood99:3063, 2002.
Xie F, Cheng F, Zhu X: Studies on hereditary deficiency of coagulation factor V.Zhonghua Xue Ye Xue Za Zhi22:453, 2001.
Zheng WD, Liu YH, Liu HF, Chen ZH, Wang Y: Identification of two novel mutations of human blood coagulation factor V gene in a Chinese family with congenital factor V deficiency. Zhonghua Yi Xue Yi Chuan Xue Za Zhi 23:515, 2006.
Yamakage N, Ikejiri M, Okumura K, et al: A case of coagulation factor V deficiency caused by compound heterozygous mutations in the factor V gene. Haemophilia 12:172, 2006.
Zhou RF, Fu QH, Xu XC, et al: Severe hereditary coagulation factor V deficiency caused by two novel heterozygous mutations. Zhonghua Xue Ye Xue Za Zhi 26:129, 2005.
Lunghi B, Castoldi E, Mingozzi F, Bernardi F: A novel factor V null mutation detected in a thrombophilic patient with pseudo-homozygous APC resistance and in an asymptomatic unrelated subject.Blood92:1463, 1998.
Vellinga S, Steel E, Vangenechten I, Gadisseur A: Successful pregnancy in a patient with factor V deficiency: Case report and review of the literature. Thromb Haemost 95:896, 2006.
Asselta R, Dall'Osso C, Duga S, Spreafico M, Saxena R, Tenchini ML: Coagulation factor V gene analysis in five Indian patients: Identification of three novel small deletions. Haematologica 91:1724, 2006.
Montefusco MC, Duga S, Asselta R, et al: A novel two base pair deletion in the factor V gene associated with severe factor V deficiency.Br J Haematol 111:1240, 2000.
Ajzner E, Balogh I, Szabo T, et al: Severe coagulation factor V deficiency caused by 2 novel frameshift mutations: 2952delT in exon 13 and 5493insG in exon 16 of factor 5 gene.Blood99:702, 2002.
Van Wijk R, Montefusco MC, Duga S, et al: Coexistence of a novel homozygous nonsense mutation in exon 13 of the factor V gene with the homozygous Leiden mutation in two unrelated patients with severe factor V deficiency.Br J Haematol114:871, 2001.
Castoldi E, Kalafatis M, Lunghi B, et al: Molecular bases of pseudo-homozygous APC resistance: The compound heterozygosity of FV R506Q and a FV null mutation results in the exclusive presence of FV Leiden molecules in plasma.Thromb Haemost80:403, 1998.
Simioni P, Scudeller A, Radossi P, et al: "Pseudo homozygous" activated protein C resistance due to double heterozygous factor V defects (factor V Leiden mutation and type I quantitative factor V defect) associated with thrombosis: Report of two cases belonging to two unrelated kindreds.Thromb Haemost 75:422, 1996.
Brugge JM, Simioni P, Bernardi F, et al: Expression of the normal factor V allele modulates the APC resistance phenotype in heterozygous carriers of the factor V Leiden mutation. J Thromb Haemost 3:2695, 2005.
Guasch JF, Cannegieter S, Reitsma PH, et al: Severe coagulation factor V deficiency caused by a 4 bp deletion in the factor V gene.Br J Haematol101:32, 1998.
Zehnder JL, Hiraki DD, Jones CD, et al: Familial coagulation factor V deficiency caused by a novel 4 base pair insertion in the factor 5 gene: Factor V Stanford.ThrombHaemost 82:1097, 1999.
Lunghi B, Scanavini D, Castoldi E, et al: The factor V Glu1608Lys mutation is recurrent in familial thrombophilia. J Thromb Haemost 3:2032, 2005.
Castoldi E, Simioni P, Kalafatis M, et al: Combinations of 4 mutations (FV R506Q, FV H1299R, FV Y1702C, PT 20210G/A) affecting the prothrombinase complex in a thrombophilic family.Blood96:1443, 2000.
Castoldi E, Lunghi B, Mingozzi F, et al: A missense mutation (Y1702C) in the coagulation factor V gene is a frequent cause of factor V deficiency in the Italian population.Haematologica86:629, 2001.
Guasch JF, Lensen RPM, Bertina RM, et al: Molecular characterization of a type I quantitative factor V deficiency in a thrombosis patient that is "pseudo homozygous" for activated protein C resistance.Thromb Haemost77:252, 1997.
Dargaud Y, Trzeciak MC, Meunier S, et al: Two novel factor V null mutations associated with activated protein C resistance phenotype/genotype discrepancy.Br J Haematol123:342, 2003.
Fu WJ, Hou J, Wang DX, Yu RQ: Identification of a novel mutation of human blood coagulation FV gene associated with congenital FV deficiency. Zhonghua Xue Ye Xue Za Zhi 24:119, 2003.
Asselta R, Montefusco MC, Duga S, et al: Severe factor V deficiency: Exon skipping in the factor V gene causing a partial deletion of the C1 domain.J Thromb Haemost1:1237, 2003.
Asselta R, Bossone A, Iannaccone L, et al: Rescue of activated protein C-resistance phenotype by cis-acting factor V Gly2032Asp mutation. Haematologica 89:761, 2004.
Asselta R, Tenchini ML, Holme R, et al: The discovery of Mary's mutation.J Thromb Heamost1:397, 2003.
Duga S, Montefusco MC, Asselta R, et al: Arg2074Cys missense mutation in the C2 domain of factor V causing moderately severe factor V deficiency: Molecular characterization by expression of the recombinant protein.Blood101:173, 2003.
Bossone A, D'Angelo F, Santacroce R, et al: Factor V Arg2074Cys: A novel missense mutation in the C2 domain of factor V.Thromb Haemost 87:923, 2002.
Schrijver I, Houissa-Kastally R, Jones CD, et al: Novel factor V C2-domain mutation (R2074H) in two families with factor V deficiency and bleeding.Thromb Haemost87:294, 2002.