BACKGROUND: Glanzmann thrombasthenia (GT) is an autosomal recessive inherited platelet function defect that is characterized by reduction in, or absence of, platelet aggregation in response to multiple physiologic agonists. The defect is caused by mutations in the genes encoding ITGA2B or ITGB3. This results in qualitative or quantitative abnormalities of the platelet receptor, alpha IIb-beta 3. OBJECTIVES: The aim of this study was to identify the mutations in GT patients and to correlate these with patient phenotype. SUBJECTS AND METHODS: A total of 45 unrelated patients with GT were enrolled in the present study to identify the causative molecular defects, and also to correlate their phenotype with their genotype. Platelet aggregation, flow cytometry, Western blotting, and mutation screening by conformation sensitive gel electrophoresis (CSGE) followed by sequencing were performed in all patients. Novel mutations were analyzed for penetrance in individual families. RESULTS: A total of 22 novel mutations were identified in 45 unrelated GT patients. Mutations were identified in 36 of the 45 (80%) patients. Missense mutations were seen in most of the GT patients (59%). The remaining mutations were heterogeneous and were distributed throughout the length of the gene. Analysis of family members showed heterozygous mutations in all families. CONCLUSIONS: The severe type I GT was the most common subtype found in this study. Missense mutations were identified as the defects responsible for most GT patients. Carrier detection and genetic counseling in these families is a potentially effective alternative for decreasing the burden of severe type of GT.
BACKGROUND:Glanzmann thrombasthenia (GT) is an autosomal recessive inherited platelet function defect that is characterized by reduction in, or absence of, platelet aggregation in response to multiple physiologic agonists. The defect is caused by mutations in the genes encoding ITGA2B or ITGB3. This results in qualitative or quantitative abnormalities of the platelet receptor, alpha IIb-beta 3. OBJECTIVES: The aim of this study was to identify the mutations in GT patients and to correlate these with patient phenotype. SUBJECTS AND METHODS: A total of 45 unrelated patients with GT were enrolled in the present study to identify the causative molecular defects, and also to correlate their phenotype with their genotype. Platelet aggregation, flow cytometry, Western blotting, and mutation screening by conformation sensitive gel electrophoresis (CSGE) followed by sequencing were performed in all patients. Novel mutations were analyzed for penetrance in individual families. RESULTS: A total of 22 novel mutations were identified in 45 unrelated GT patients. Mutations were identified in 36 of the 45 (80%) patients. Missense mutations were seen in most of the GT patients (59%). The remaining mutations were heterogeneous and were distributed throughout the length of the gene. Analysis of family members showed heterozygous mutations in all families. CONCLUSIONS: The severe type I GT was the most common subtype found in this study. Missense mutations were identified as the defects responsible for most GT patients. Carrier detection and genetic counseling in these families is a potentially effective alternative for decreasing the burden of severe type of GT.
Authors: L Zhou; M Jiang; H Shen; T You; Z Ding; Q Cui; Z Ma; F Yang; Z Xie; H Shi; J Su; L Cao; J Lin; J Yin; L Dai; H Wang; Z Wang; Z Yu; C Ruan; L Xia Journal: Clin Genet Date: 2018-05-22 Impact factor: 4.438
Authors: Isabel Sánchez-Guiu; Ana I Antón; José Padilla; Francisco Velasco; José F Lucia; Miguel Lozano; Ana Rosa Cid; Teresa Sevivas; María F Lopez-Fernandez; Vicente Vicente; Consuelo González-Manchón; José Rivera; María L Lozano Journal: Orphanet J Rare Dis Date: 2014-12-24 Impact factor: 4.123