Two new beta3 integrin mutations in Indian patients with Glanzmann thrombasthenia: localization of mutations affecting cysteine residues in integrin beta3.
New mutations in the beta3 integrin subunit have been identified in two unrelated Glanzmann thrombasthenia patients originating from India and Bangladesh. Both patients had histories of excessive bleeding and were found to have Glanzmann thrombasthenia based on absent ADP-induced platelet aggregation. Immunoblotting of platelet lysates of Patient 1 demonstrated reduced levels of alphaIIb and an unexpected high Mr beta3 band of approximately 260,000, with little or no normal-sized beta3. Upon reduction, a weak beta3 band of normal Mr was observed. Platelet lysates of Patient 2 demonstrated undetectable levels of beta3. Sequence analyses identified homozygous mutations in the beta3 genes of both patients. Patient 1 had a C506Y missense mutation resulting in the expression of an unpaired cysteine; we propose that the Mr approximately 260,000 band is a disulfide-bonded beta3 dimer. Patient 2 had an insertion mutation resulting in a frameshift and premature termination. Both mutations affect biogenesis of platelet alphaIIbbeta3 receptors.
D000328:Adult; D001792:Blood Platelets / Q000737:chemistry; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D004220:Disulfides; D005192:Family Health; D005260:Female; D016368:Frameshift Mutation; D006720:Homozygote; D006801:Humans; D007194:India; D039661:Integrin beta3 / Q000032:analysis / Q000737:chemistry / Q000235:genetics*; D008297:Male; D009154:Mutation; D020125:Mutation, Missense; D040201:Platelet Membrane Glycoprotein IIb / Q000032:analysis; D011487:Protein Conformation; D013915:Thrombasthenia / Q000175:diagnosis / Q000235:genetics*
D004220:Disulfides; D039661:Integrin beta3; D040201:Platelet Membrane Glycoprotein IIb