title: The first case of combined coagulation factor V and coagulation factor VIII deficiency in Poland due to a novel p.Tyr135Asn missense mutation in the MCFD2 gene.
abstract: Congenital combined coagulation factor V and coagulation factor VIII deficiency (F5F8D) is a rare bleeding disorder due to mutations in the LMAN1 or MCFD2 genes. Here we report the first Polish family with F5F8 deficiency due to a mutation in the MCFD2 gene. The proposita suffered from mild bleeding including epistaxis, menorrhagia, bleeding after dental extraction, and bruising after minor traumas. The F5F8 deficiency was diagnosed due to an excessive postpartum bleeding at the age of 31. Analysis of further family members revealed a second affected individual. Sequencing of the MCFD2 gene and its flanking regions in both patients demonstrated a novel homozygous missense mutation within the second elongation factor hand domain resulting in a substitution of tyrosine by asparagine at amino acid position 135 (p.Tyr135Asn). This variant represents the third missense mutation found in the MCFD2 gene and most likely disrupts the MCFD2-LMAN1 interaction, thus leading to the disease phenotype.
authors.affiliation: Institute of Experimental Haematology and Transfusion Medicine, University Clinic Bonn, Bonn, Germany. vytautas.ivaskevicius@ukb.uni-bonn.de
authors.forename: Vytautas
authors.initials: V
authors.lastname: Ivaskevicius
authors.forename: Jerzy
authors.initials: J
authors.lastname: Windyga
authors.forename: Beata
authors.initials: B
authors.lastname: Baran
authors.forename: Ksenia
authors.initials: K
authors.lastname: Bykowska
authors.forename: Laurynas
authors.initials: L
authors.lastname: Daugela
authors.forename: Matthias
authors.initials: M
authors.lastname: Watzka
authors.forename: Erhard
authors.initials: E
authors.lastname: Seifried
authors.forename: Johannes
authors.initials: J
authors.lastname: Oldenburg
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D017124:Conserved Sequence; D005166:Factor V Deficiency / Q000235:genetics*; D005260:Female; D006467:Hemophilia A / Q000235:genetics*; D006801:Humans; D037241:Mannose-Binding Lectins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010375:Pedigree; D017354:Point Mutation; D011044:Poland; D006473:Postpartum Hemorrhage / Q000235:genetics; D011247:Pregnancy; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D033921:Vesicular Transport Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: C084004:LMAN1 protein, human; C475146:MCFD2 protein, human; D037241:Mannose-Binding Lectins; D008565:Membrane Proteins; D033921:Vesicular Transport Proteins