Combined factor V – factor VIII deficiency (F5F8D): Compound heterozygosity for two novel truncating mutations in LMAN1 in a consanguineous patient

Roula A. Farah; Philippe de Moerloose; Isabelle Bouchardy; Michael A. Morris; Wadad Barakat; Alain E. Sayad; Marguerite Neerman-Arbez

doi:10.1160/TH06-01-0051

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2006; 95(05): 893-895
DOI: 10.1160/TH06-01-0051

Case Report

Schattauer GmbH

Combined factor V – factor VIII deficiency (F5F8D): Compound heterozygosity for two novel truncating mutations in LMAN1 in a consanguineous patient

Roula A. Farah

¹Departments of Pediatrics and Laboratory Medicine, Rizk Hospital, Beirut, Lebanon

,

Philippe de Moerloose

²Division of Angiology and Hemostasis, University Hospitals, Geneva, Switzerland

,

Isabelle Bouchardy

³Molecular Diagnostic Laboratory, Service of Medical Genetics, University Hospitals, Geneva, Switzerland

,

Michael A. Morris

³Molecular Diagnostic Laboratory, Service of Medical Genetics, University Hospitals, Geneva, Switzerland

,

Wadad Barakat

¹Departments of Pediatrics and Laboratory Medicine, Rizk Hospital, Beirut, Lebanon

,

Alain E. Sayad

¹Departments of Pediatrics and Laboratory Medicine, Rizk Hospital, Beirut, Lebanon

,

Marguerite Neerman-Arbez

²Division of Angiology and Hemostasis, University Hospitals, Geneva, Switzerland

⁴Department of Genetic Medicine and Development, University Medical School, Geneva, Switzerland

› Author Affiliations

Abstract

Full Text

References

References
1 Oeri J, Matter M, Isenschmid H. et al. Congenital factor V deficiency (parahemophilia) with true hemophilia in two brothers. Bibl Paediatr 1954; 58: 575-88.
2 Seligsohn U, Ramot B. Combined factor-V and factor-VIII deficiency: report of four cases. Br J Haematol 1969; 16: 475-86.
3 Seligsohn U, Zivelin A, Zwang E. Combined factor V and factor VIII deficiency among non-Ashkenazi Jews. N Engl J Med 1982; 307: 1191-5.
4 Sweeney J, Wenz B. Combined factor V and factor VIII deficiency. N Engl J Med 1983; 308: 656-7.
5 Peyvandi F, Tuddenham EG, Akhtari AM. et al. Bleeding symptoms in 27 Iranian patients with the combined deficiency of factor V and factor VIII. Br J Haematol 1998; 100: 773-6.
6 Nichols WC, Seligsohn U, Zivelin A. et al. Linkage of combined factors V and VIII deficiency to chromosome 18q by homozygosity mapping. J Clin Invest 1997; 99: 596-601.
7 Neerman-Arbez M, Antonarakis SE, Blouin JL. et al. The locus for combined factor V-factor VIII deficiency (F5F8D) maps to 18q21, between D18S849 and D18S1103. AmJ Hum Genet 1997; 61: 143-50.
8 Nichols WC, Seligsohn U, Zivelin A. et al. Mutations in the ER-Golgi intermediate compartment protein ERGIC-53 cause combined deficiency of coagulation factors V and VIII. Cell 1998; 93: 61-70.
9 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 1999; 93: 2253-60.
10 Nichols WC, Terry VH, Wheatley MA. et al. ERGIC-53 gene structure and mutation analysis in 19 combined factors V and VIII deficiency families. Blood 1999; 93: 2261-6.
11 Zhang B, Cunningham MA, Nichols WC. et al. Bleeding due to disruption of a cargo-specific ER-to-Golgi transport complex. Nat Genet 2003; 34: 220-5.
12 Zhang B, Kaufman RJ, Ginsburg D. LMAN1 and MCFD2 form a cargo receptor complex and interact with coagulation factor VIII in the early secretory pathway. J Biol Chem 2005; 280: 25881-6.
13 Antonarakis SE. Recommendations for a nomenclature system for human gene mutations. Nomenclature Working Group. Hum Mutat 1998; 11: 1-3.
14 Sirachainan N, Zhang B, Chuansumrit A. et al. Combined factor V and factor VIII deficiency ina Thai patient: a case report of genotype and phenotype characteristics. Haemophilia 2005; 11: 280-4.
15 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 2005; 79: 262-6.
16 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 2006; 107: 1903-7.
17 Zhang B, Ginsburg D. Familial multiple coagulation factor deficiencies: new biologic insight from rare genetic bleeding disorders. J Thromb Haemost 2004; 02: 1564-72.
18 Nufer O, Kappeler F, Guldbrandsen S. et al. ER export of ERGIC-53 is controlled by cooperation of targeting determinants in all three of its domains. J Cell Sci 2003; 116: 4429-40.