Modulation of clinical phenotype of Glanzmann's thrombasthenia by thrombogenic mutations.
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.
Kannan
Meganathan
M
Department of Hematology, All India Institute of Medical Sciences, New Delhi, India.
Yadav
Birendra Kumar
BK
Ahmad
Firdos
F
Biswas
Arijit
A
Saxena
Renu
R
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
D016824:Antigens, Human Platelet; D001779:Blood Coagulation Factors; D005340:Fibrinogen