title: Congenital combined deficiency of coagulation factors VII and X--different genetic mechanisms.
abstract: Combined coagulation factor VII (FVII) and factor X (FX) deficiency (combined FVII/FX deficiency) belongs to the group of bleeding disorders in which both factors show reduced plasma activity. It may arise from coincidental inheritance of separate coagulation factor deficiencies or a common cause as large deletions comprising both gene loci. The F7 and F10 genes are located on the long arm of chromosome 13. Here, we describe 10 cases with combined FVII/FX deficiency representing both genetic mechanisms of occurrence. Genetic analyses included direct sequencing of the F7 and F10 genes and MLPA (multiplex ligation-dependent probe amplification) for detection of heterozygous large deletions. In four patients, the combined deficiency was due to a large deletion within the terminal end of chromosome 13. In the remaining six cases the deficiency resulted from coincidental inheritance of different genetic alterations affecting both genes independently. In most cases, the genetic defects were heterozygous, presenting with prolonged PT, normal aPTT and mild or no bleeding symptoms. Only in one case compound heterozygous mutations were detected in the F10, resulting in prolonged aPTT and a more severe bleeding phenotype. To avoid a misdiagnosis of combined FVII/FX deficiency, analyses of single factor activities have to be performed in all cases with prolonged PT even if aPTT is normal. Genetic analyses are substantial for correct prediction of an inheritance pattern and a proper genetic counselling.
authors.affiliation: Institute of Experimental Haematology and Transfusion Medicine, University Clinic Bonn, Bonn, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Pavlova
authors.affiliation: Institute of Experimental Haematology and Transfusion Medicine, University Clinic Bonn, Bonn, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Preisler
authors.affiliation: Institute of Experimental Haematology and Transfusion Medicine, University Clinic Bonn, Bonn, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Driesen
authors.affiliation: Division of Angiology and Haemostasis, University Hospital and Faculty of Medicine, Geneva, Switzerland.
authors.forename: P
authors.initials: P
authors.lastname: de Moerloose
authors.affiliation: Department of Pediatrics and Adolescent Medicine, University of Freiburg, Freiburg, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Zieger
authors.affiliation: Department of Pediatric Haematology and Oncology, Dr. von Hauner Children's Hospital, Ludwig-Maximilians-University Munich, Munich, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Hütker
authors.affiliation: Medical Laboratory Bremen, Bremen, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Dengler
authors.affiliation: Institute of Experimental Haematology and Transfusion Medicine, University Clinic Bonn, Bonn, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Harbrecht
authors.affiliation: Institute of Experimental Haematology and Transfusion Medicine, University Clinic Bonn, Bonn, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Oldenburg
mesh_terms: D001780:Blood Coagulation Tests; D002872:Chromosome Deletion; D002882:Chromosomes, Human, Pair 13; D005167:Factor VII / Q000235:genetics*; D005168:Factor VII Deficiency / Q000150:complications* / Q000175:diagnosis / Q000235:genetics*; D005170:Factor X / Q000235:genetics*; D005171:Factor X Deficiency / Q000150:complications* / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D006579:Heterozygote; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D010641:Phenotype
chemical_list: D005167:Factor VII; D005170:Factor X
keywords: chromosome 13 deletion; factor VII deficiency; factor X deficiency; familial multiple coagulation factor deficiencies