title: Modulation of clinical phenotype of Glanzmann's thrombasthenia by thrombogenic mutations.
abstract: BACKGROUND
  Glanzmann's thrombasthenia (GT) is an autosomal recessive bleeding disorder which is due to a defect in platelet aggregation in response to multiple physiological agonists. It has been demonstrated that the clinical phenotype of various diseases inherited in a classic Mendelian fashion can be modulated by a series of factors, inherited as well as acquired.
  
  
  METHODS
  A total of 45 GT patients were screened for the thrombogenic polymorphisms, i.e., FV Leiden (R506Q), Prothrombin G20210A, MTHFR C677T and HPA-1 by PCR/RFLP.
  
  
  RESULTS
  MTHFR C677T heterozygous was seen in 6 patients, FV Leiden heterozygous in one and Prothrombin G20210A gene variant in none. HPA-1 was seen in 3 patients of whom 1 was homozygous and 2 were heterozygous.
  
  
  CONCLUSIONS
  Thus the coinheritance of heterozygous FV Leiden alone or homozygous HPA 1b alone or the combined heterozygosity of MTHFR and HPA-1 were predicted to alter the clinical phenotype. Whereas the inheritance of heterozygous MTHFR alone or heterozygous HPA-1 alone did not altered the clinical phenotype significantly. Hence FV Leiden, MTHFR C677T polymorphism along with PLA-1 and homozygous HPA-1 were the probable ameliorating factor in GT mild phenotype.
authors.affiliation: Department of Hematology, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Meganathan
authors.initials: M
authors.lastname: Kannan
authors.forename: Birendra Kumar
authors.initials: BK
authors.lastname: Yadav
authors.forename: Firdos
authors.initials: F
authors.lastname: Ahmad
authors.forename: Arijit
authors.initials: A
authors.lastname: Biswas
authors.forename: Renu
authors.initials: R
authors.lastname: Saxena
mesh_terms: D016824:Antigens, Human Platelet / Q000235:genetics; D001779:Blood Coagulation Factors / Q000235:genetics*; D001803:Blood Transfusion; D004844:Epistaxis / Q000473:pathology; D005340:Fibrinogen / Q000378:metabolism; D006720:Homozygote; D006801:Humans; D009154:Mutation; D010641:Phenotype; D010974:Platelet Aggregation; D011110:Polymorphism, Genetic; D013915:Thrombasthenia / Q000235:genetics* / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology
chemical_list: D016824:Antigens, Human Platelet; D001779:Blood Coagulation Factors; D005340:Fibrinogen