Identification of 22 novel mutations in patients with Glanzmann's thrombasthenia

Glanzmann's thrombasthenia (GT) is an autosomal recessive inherited platelet function defect that characterized by reduction in, or absence of, platelet aggregation in response to multiple physiologic agonists. GT is characterized by normal platelet count, prolonged bleeding time, and abnormal clot retraction. The defect is caused by mutations in the genes encoding GPIIb or GPIIIa that result in qualitative or quantitative abnormalities of the platelet membrane GPIIb/IIIa. GT occurs in high frequency in certain ethnic populations with an increased incidence of consanguinity, such as Indians, Iranians, Iraqi Jews, Palastinian and Jordanian Arabs and French gypsies. Forty-five unrelated patients of GT were enrolled in the study to identify the causative molecular defects and also to correlate the genotype with the phenotype. Molecular modeling was performed for the novel missense mutations. The current study identifies 22 novel mutations in these patients. Missense mutations were identified as the defects responsible for most of the GT patients (59%). Even though missense was common, the study concludes that the genetic defect is heterogeneous in nature and difficult to design a DNA marker for carrier detection in GT

Role of MTHFR C677T polymorphism in ischemic stroke

Background: Homozygosity for MTHFR C677T polymorphism can lead to significantly high homocysteine levels and hyperhomocysteinemia is an important risk factor for thrombotic events. Aims: The aim was to determine role of MTHFR C677T polymorphism in North Indians with ischemic stroke. Settings and Design: In a prospective study, the subjects of stroke were recruited from the neurology clinic of the hospital. Controls were healthy individuals from the Hematology clinic without any history of stroke. Materials and Methods: Plasma homocysteine levels were measured by enzyme immuno assay method after 3 months of acute episode. Serum folate and Vitamin B12 levels were estimated by competitive inhibition radioassay. MTHFR polymorphism was detected by PCR-RFLP using Hinf I enzyme. Statistical analysis: The analysis of significance of results was done using SPSS software package. A pvalue < 0.05 was taken as significant. Results: Thirty-two acute ischemic stroke patients (aged 1-44 years) were studied. Fourteen (43.8%) had recurrent stroke. Nine (28%) had multiple infarcts. Four of 32 patients (12.5%) had high homocysteine levels. Three out of these 4 hyper-homocysteinemia patients were homozygous ( TT ) for MTHFR polymorphism (2 with recurrent stroke). Two of three homozygous cases with TT genotype had low serum folate. Five of 32 stroke cases (18.8%) were heterozygous ( CT ) genotype. Conclusions: Primary hyper-homocysteinemia appears to be an important risk factor for ischemic stroke in North Indians, most due to MTHFR C677T homozygosity. Folate levels may modify the presentation of the MTHFR TT genotype