[Molecular analysis of gene mutations in eight patients with Glanzmann's thrombasthenia]

Objective: To analyze the gene sequencing in eight patients with Glanzmann's thromboasthenia(GT), and combined with clinical manifestations and laboratory findings to investigate the molecular mechanism of GT. Methods: Eight patients who were diagnosed as GT based on platelet aggregation test and flow cytometry were enrolled, as well as 4 pedigrees. Next-generation sequencing was used to analyze all the exons and flanking sequences of αⅡ band β3 gene and also platelet-type bleeding disorders related genes. Gene polymorphism was excluded by retrievaling HGMD and PubMed databases and relative literature. Mutations were confirmed by sanger sequencing. Results: All the eight patients had relatively normal platelet counts and coagulation profiles. But their platelet response to ADP was impaired, and their platelet response to ristocetin was relatively normal. Flow cytometry showed that of the 8 patients, platelet surface αⅡb/β3 was lower than 5% of the normal value in 5 cases, and in 2 cases was 5% to 20% of normal value, and in 1 case there was no significant platelet surface αⅡb/β3 reduction compared with normal level. Gene analysis revealed that five mutations in ITGA2B gene were identified, including c. 1750C>T(p.Arg584Ter), c.1882C>T(p.Arg628Ter), c.814G>C(p.Val272Leu), c.2333A>C(p.Gln778Pro), c.432G>A(p.Trp144Ter). Six mutations in ITGB3 gene, including c. 719G>A(p.Arg240Gln), c.2248C>T(p.Arg750Ter), c.1495T>C(p.Cys499Arg), c.1728delC(p.Ser577ProfsTer92), c.877C>T(p.Gln293Ter), c. 1260G>A were identified. In addition, mutations in genes such as RUNX1, HPS4, MYH9, ACTN1, HPS3 and SETBP1 were identified in patients with GT. Conclusions: Rather than homozygous mutations, heterozygous mutations, especially compound heterozygous mutations, are more common in patients with GT. The pathogenesis of GT may relate to gene mutations such as RUNX1 in addition to the ITGA2B gene and the ITGB3 gene.