2007 Mutations in patients with combined factor V and VIII deficiency

Mutations in patients with combined factor V and VIII deficiency

Gene	Mutation	Location	Type	Genotype	Origin	comments	Reference
LMAN1	Met1Thr*	Exon 1	Initiation codon	Hom	Italy		1, 2, 3
LMAN1	nt 23 del G	Exon 1	Frameshift	Hom	Iran		2
LMAN1	nt 31 del G	Exon 1	Frameshift	Hom	Algeria		2
LMAN1	nt 89 ins G*	Exon 1	Frameshift	Hom	Middle Eastern Jewish	Founder effect	1, 2, 4, 5
LMAN1	nt 89 ins G*	Exon 1	Frameshift	Hom	Iran		2
LMAN1	nt 89 ins G* nt 912 ins A*	Exon 1 Exon 8	Frameshift Frameshift	Comp het	Iran		2
LMAN1	Gly114stop	Exon 2	Nonsense	Hom	India		6
LMAN1	nt 422 del C Undefined	Exon 3	Frameshift	Comp het	Japan		1
LMAN1	Arg202stop*	Exon 5	Nonsense	Hom	Japan		1, 7
LMAN1	Arg202stop*	Exon 5	Nonsense	Hom	Iran		2
LMAN1	IVS5+1G>T	Intron 5	Splicing	Hom	Italy		2
LMAN1	nt 720 del 16bp	Exon 6	Frameshift	Hom	Venezuela		1
LMAN1	nt781 del T	Exon 7	Frameshift	Hom	Austria		3
LMAN1	nt 822 G>A	Exon 7	Splicing	Hom	Iran		2
LMAN1	IVS7+1 G>A	Intron 7	Splicing	Hom	Belgium		3
LMAN1	IVS7+33 ins GGTT Undefined	Intron 7	Splicing	Comp het	USA	Skipping exon 8	3
LMAN1	IVS7-1 G>C Arg456stop*	Intron 7 Exon 11	Splicing Nonsense	Comp het	Thailand		8
LMAN1	nt 841 del A	Exon 8	Frameshift	Hom	Poland		3
LMAN1	Lys302stop*	Exon 8	Nonsense	Hom	Pakistan		2
LMAN1	Lys302stop*	Exon 8	Nonsense	Hom	France		1
LMAN1	nt 912 ins A*	Exon 8	Frameshift	Hom	Iran		2
LMAN1	Glu321stop	Exon 9	Nonsense	Hom	Iraq		3
LMAN1	nt 1109 del TC	Exon 9	Frameshift	Hom	USA		1
LMAN 1	Gln380stop nt 1271 del G	Exon 9 Exon 11	Nonsense Splicing	Comp het	Lebanon		9
LMAN1	IVS9+2 T>G	Intron 9	Splicing	Hom	Iran		2
LMAN1	IVS9+2 T>C*	Intron 9	Splicing	Hom	Tunisian Jewish	Founder effect	1, 4, 5, 10
LMAN1	nt 1208 ins T	Exon 10	Frameshift	Hom	Italy		2
LMAN1	nt 1214 del 5 bp	Exon 10	Frameshift	Hom	Iran		2
LMAN1	Arg456stop*	Exon 11	Nonsense	Hom	China		2
LMAN1	Arg456stop*	Exon 11	Nonsense	Hom	Pakistan		2
LMAM1	Cys475Arg Undefined	Exon 12	Missense	Comp het	Argentina	Italian origin	3
LMAN1	nt 1524 del A	Exon 13	Frameshift	Hom	USA (Armenian)		1

MCFD2	IVS1-1 G>C	Intron 1	Splicing	Hom	Iran		3
MCFD2	IVS2+5 G>A*	Intron 2	Splicing	Hom	Undefined, Italy, India, Serbia	Different haplotypes	3, 6, 11
MCFD2	IVS3+1 G>A*	Intron 3	Splicing	Hom			11
MCFD2	nt 103 del C	Exon 2	Frameshift	Hom			11
MCFD2	nt 249 del T	Exon 3	Frameshift	Hom			11
MCFD2	nt 263 del 8 bp	Exon 3	Frameshift	Hom			11
MCFD2	Asp89Ala	Exon 3	Missense	Hom			3
MCFD2	Asp129Glu	Exon 4	Missense	Hom			11
MCFD2	Ile136Thr*	Exon 4	Missense	Hom	Undefined, Kosovo		3, 11

Nucleotide numbers of LMAN1 are based on the Genebank file X716661 using the A (nt 22) of the ATG initiation methionine as +1.
Nucleotide numbers of MCFD2 are based on the Genebank file NM_139279 using the A (nt 90) of the ATG initiation methionine as +1.
*A mutation that was identified in more than 1 family.

References

Nichols WC, Terry VH, Wheatley MA, et al: ERGIC-53 gene structure and mutation analysis in 19 combined factors V and VIII deficiency families.Blood93:2261, 1999.
Neerman-Arbez M, Johnson KM, Morris MA, et al: Molecular analysis of the ERGIC-53 gene in 35 families with combined factor V-Factor VIII deficiency.Blood 93:2253, 1999.
Zhang B, McGee B, Yamaoka JS, et al: Combined deficiency of factor V and factor VIII is due to mutations in either LMAN1 or MCFD2. Blood, 107:1903, 2006.
Nichols WC, Seligsohn U, Zivelin A, et al: Mutations in the ER-Golgi intermediate compartment protein ERGIC-53 cause combined deficiency of coagulation factorsV and VIII.Cell93:61, 1998.
Nichols WC, Seligsohn U, Zivelin A, et al: Linkage of combined factors V and VIII deficiency to chromosome 18q by homozygosity mapping.J Clin Invest99:596, 1997.
Mohanty D, Ghosh K, Shetty S, et al: Mutations in the MCFD2 gene and a novel mutation in the LMAN1 gene in Indian families with combined deficiency of factor V and VIII. Am J Hematol 79:262, 2005.
Dansako H, Ishimaru F, Takai Y, et al: Molecular characterization of the ERGIC-53 gene in two Japanese patients with combined factor V-factor VIII deficiency.Ann Hematol80:292, 2001.
Sirachainan N, Zhang B, Chuansumrit A, et al: Combined factor V and factor VIII deficiency in a Thai patient: a case report of genotype and phenotype characteristics. Haemophilia 11:280, 2005.
Farah RA, De Moerloose P, Bouchardy I, et al: Combined factor V – factor VIII deficiency (F5F8D): Compound heterozygosity for two novel truncating mutations in LMANI in a consanguineous patient. Thromb Haemost 95:893, 2006.
Segal A, Zivelin A, Rosenberg N, et al: A mutation in LMAN1 (ERGIC-53) causing combined factor V and factor VIII deficiency is prevalent in Jews originating from the island of Djerba in Tunisia.Blood Coagul Fibrinolysis15:99, 2004.
Zhang B, Cunningham MA, Nichols WC, et al: Bleeding due to disruption of a cargo-specific ER-to-Golgi transport complex.Nat Genet34:220, 2003.