Identification of one novel pathogenic ITGB3 mutation and two known mutations in two Chinese pedigrees with hereditary Glanzmann thrombasthenia

Abstract

Glanzmann thrombasthenia (GT) is an inherited disorder of platelet aggregation resulting from quantitative and/or qualitative abnormalities of the glycoprotein IIb/IIIa complex. We analyzed the expression of GPIIb/IIIa and the gene sequencing in two pedigrees with GT, so as to determine the type and the relationship between genotype and clinical phenotype. Platelet aggregation tests and flow cytometric studies were performed, along with gene sequencing. Both probands were classified as grade III of bleeding. Platelet aggregation was absent or defective upon stimulation with physiological stimuli like AA and ADP, but platelets agglutinated normally in response to ristocetin. MFI values were considerably reduced. Gene sequencing showed ITGB3 mutations p.Cys549Ser/p.Leu705CysfsTer4 in proband 1 and p.Cys549Ser/p.Gln254Lys in proband 2 and her sister. This study reports one novel ITGB3 mutant gene, p.Gln254Lys, of which we will explore the potential pathogenicity.

Keywords:

• Glanzmann thrombasthenia (GT)
• GPIIb/IIIa
• ITGB3
• novel mutation

Acknowledgements

All authors’ excellent contributions to the work: Zhengjing Lu, Lauriane Nikuze Hongying Wei and accomplished the experiment, analyzed the results, drafted and revised the article; Zhoulin Zhong, accomplished the experiment and designed figures; Fang Li constructed the crystal structure of ${\alpha }_{IIb}{\beta }_3$ and analyzed the Gln254Lys mutation. Kairong Liang and Manlv Wei, collected complete histories and clinical data. All authors gave final approval of the manuscript. We are grateful to Dr. Ma (Guangxi National Hospital, Nanning, Guangxi Zhuang Autonomous Region, China) and Beijing Kangso Medical Inspection for helpful technical support.

Disclosures

The authors have no conflict of interest.

Additional information

Funding

This study was supported by grants from the Natural Science Foundation of Guangxi Province (No.2016GXNSFAA380161). All authors’ excellent contributions to the work.