title: Mutations in GPIIIa molecule as a cause for Glanzmann thrombasthenia in Indian patients.
abstract: BACKGROUND
  Glanzmann thrombasthenia (GT) results from a quantitative or qualitative defect of GPIIb-IIIa complex, the fibrinogen receptor on platelets, which plays a very important role in platelet aggregation. In this report we describe the molecular studies on 22 patients with Glanzmann Thrombasthenia at our institute.
  
  
  OBJECTIVE
  The main objective was to identify the mutations present in our GT population in order to establish a strategy for genetic counseling and antenatal diagnosis.
  
  
  METHODS
  Twenty-two patients with GT were included in the present study. Complete blood count (CBC), platelet aggregation, flow cytometry, Western blot, single strand conformation polymorphism (SSCP) and denaturing gradient gel electrophoresis (DGGE) were performed in all the patients. The patients showing an abnormal migration pattern in SSCP or DGGE were sequenced further on an automated sequencer.
  
  
  RESULTS
  Of the 22 patients studied, mutations were detected in 12 individuals. Of these, 11 were novel mutations and one mutation Y115C was reported earlier. Flow cytometric analysis showed the absence of receptors in type I GT, highly reduced levels in type II GT and normal levels in type III GT. The DGGE analysis and SSCP analysis of the patients showed different migration patterns. Sequencing was performed in all patients showing an abnormal migration pattern. Of the 22 cases studied mutations could be detected in 12 cases of GT. We could detect six patients with point mutations, four patients with insertions and five patients with deletion mutations. Exon 4 has been found to be the most common site for mutations in our patients.
  
  
  CONCLUSIONS
  This study has shown a wide array of mutations present in our GT patients which would be extremely useful in genetic counseling and prenatal diagnosis, essential in preventing these disorders in succeeding generations.
authors.affiliation: Institute of Immunohaematology (ICMR), 13th floor, New Building, KEM Hospital, Parel, Mumbai 400012, India.
authors.forename: S
authors.initials: S
authors.lastname: Nair
authors.forename: K
authors.initials: K
authors.lastname: Ghosh
authors.forename: S
authors.initials: S
authors.lastname: Shetty
authors.forename: D
authors.initials: D
authors.lastname: Mohanty
mesh_terms: D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D006801:Humans; D007194:India; D039661:Integrin beta3 / Q000235:genetics*; D008297:Male; D016254:Mutagenesis, Insertional; D009154:Mutation; D017354:Point Mutation; D017384:Sequence Deletion; D013915:Thrombasthenia / Q000209:etiology / Q000235:genetics*
chemical_list: D039661:Integrin beta3