title: Frequency of the p.Gly262Asp mutation in congenital Factor X deficiency.
abstract: BACKGROUND
  Congenital factor X (FX) deficiency is a rare bleeding disorder inherited as an autosomal recessive trait with an incidence of 1 : 500 000-1 000 000. A total or partial deficiency of FX causes an impairment of clot formation, leading to a haemorrhagic disease, which manifests with bleeding symptoms of different severity, also unprovoked.
  
  
  OBJECTIVE
  We analysed the clinical manifestations, laboratory phenotype and genotype in 12 patients from Turkey affected with severe FX deficiency.
  
  
  METHODS
  Prothrombin time (PT), activated partial thromboplastin time (APTT), FX activity (FX:C) and FX antigen level (FX:Ag) were measured, and mutation analysis was performed for all patients.
  
  
  RESULTS
  The most frequent bleeding episodes in patients were epistaxis and easy bruising (11/12, 91%), followed by haemarthroses (10/12, 83%). FX:C was <1% in 11 patients, and 4% in one. FX:Ag was reduced in all patients, consistent with type II deficiency. Direct sequencing of the factor X gene (F10) identified two different mutations: the novel 33 bp in-frame deletion p.Thr176_Gln186, c.526_558del, which seems to be associated with milder bleeding symptoms and the c.785G>A, p.Gly262Asp missense mutation (previously reported as Gly222Asp), which is associated with severe bleeding symptoms.
  
  
  CONCLUSIONS
  The p.Gly262Asp missense mutation was identified in 11 of the 12 patients in this study. Previously published cases on the same p.Gly262Asp mutation were Iranian patients originating from the border between Turkey and Iran suggesting that this mutation may be candidate as a good tool for mutational screening analysis in this area.
authors.affiliation: Department of Pediatrics and Pediatric Cardiology, Ipekyolu Women's and Children's Hospital, Van, Turkey.
authors.forename: Serdar
authors.initials: S
authors.lastname: Epcacan
authors.affiliation: Angelo Bianchi Bonomi Hemophilia and Thrombosis Centre, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Department of Pathophysiology and Transplantation, Università degli Studi di Milano, and Fondazione Luigi Villa, Milan, Italy.
authors.forename: Marzia
authors.initials: M
authors.lastname: Menegatti
authors.affiliation: Department of Pediatric Hematology and Oncology, Faculty of Medicine, Yuzuncu Yil University, Van, Turkey.
authors.forename: Sinan
authors.initials: S
authors.lastname: Akbayram
authors.affiliation: Angelo Bianchi Bonomi Hemophilia and Thrombosis Centre, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Department of Pathophysiology and Transplantation, Università degli Studi di Milano, and Fondazione Luigi Villa, Milan, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Cairo
authors.affiliation: Angelo Bianchi Bonomi Hemophilia and Thrombosis Centre, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Department of Pathophysiology and Transplantation, Università degli Studi di Milano, and Fondazione Luigi Villa, Milan, Italy.
authors.forename: Flora
authors.initials: F
authors.lastname: Peyvandi
authors.affiliation: Department of Pediatric Hematology and Oncology, Faculty of Medicine, Yuzuncu Yil University, Van, Turkey.
authors.forename: Ahmet F
authors.initials: AF
authors.lastname: Oner
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005171:Factor X Deficiency / Q000151:congenital / Q000235:genetics*; D005260:Female; D005838:Genotype; D006470:Hemorrhage / Q000235:genetics*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D020125:Mutation, Missense / Q000235:genetics*; D010641:Phenotype; D014421:Turkey / Q000208:ethnology; D055815:Young Adult
keywords: Factor X; Factor X deficiency; genotype-phenotype association; haemorrhage; rare bleeding disorders