Clinical and Molecular Insights into Glanzmann's Thrombasthenia in China

Overview

Journal Clin Genet

Specialty Genetics

Date 2018 Apr 21

PMID 29675921

Citations 6

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

Affiliations

Soon will be listed here.

Abstract

Glanzmann's thrombasthenia (GT) is a rare bleeding disorder characterized by spontaneous mucocutaneous bleeding. The disorder is caused by quantitative or qualitative defects in integrin αIIbβ3 (encoded by ITGA2B and ITGB3) on the platelet and is more common in consanguineous populations. However, the prevalence rate and clinical characteristics of GT in non-consanguineous populations have been unclear. We analyzed 97 patients from 93 families with GT in the Han population in China. This analysis showed lower consanguinity (18.3%) in Han patients than other ethnic populations in GT-prone countries. Compared with other ethnic populations, there was no significant difference in the distribution of GT types. Han females suffered more severe bleeding and had a poorer prognosis. We identified a total of 43 different ITGA2B and ITGB3 variants, including 25 previously unidentified, in 45 patients. These variants included 14 missense, 4 nonsense, 4 frameshift, and 3 splicing site variants. Patients with the same genotype generally manifested the same GT type but presented with different bleeding severities. This suggests that GT clinical phenotype does not solely depend on genotype. Our study provides an initial, yet important, clinical and molecular characterization of GT heterogeneity in China.

Citing Articles

Epidemiological and clinical characteristics of children and young adults with Glanzmann's thrombasthenia in upper Egypt: a multicenter cross-sectional study.

Khalifa G, El-Sayed A, Elmasry Z, Elsayh K, Atwa Z, Morgan D Ann Hematol. 2025; .

PMID: 40074839 DOI: 10.1007/s00277-025-06290-5.

Clinical Management of a Rare Hereditary Bleeding Disorder in an Adult: Glanzmann Thrombasthenia.

Mecca R, Senthil N, Lakshmanan S, Anna Anil A Cureus. 2024; 16(10):e72391.

PMID: 39588442 PMC: 11586241. DOI: 10.7759/cureus.72391.

Eptifibatide, an Older Therapeutic Peptide with New Indications: From Clinical Pharmacology to Everyday Clinical Practice.

Tonin G, Klen J Int J Mol Sci. 2023; 24(6).

PMID: 36982519 PMC: 10049647. DOI: 10.3390/ijms24065446.

Glanzmann Thrombasthenia in Pakistani Patients: Identification of 7 Novel Pathogenic Variants in the Fibrinogen Receptor αIIbβ3.

Siddiqi M, Boeckelmann D, Naz A, Imran A, Ahmed S, Najmuddin A Cells. 2023; 12(2).

PMID: 36672149 PMC: 9856889. DOI: 10.3390/cells12020213.

Profiling the Genetic and Molecular Characteristics of Glanzmann Thrombasthenia: Can It Guide Current and Future Therapies?.

Nurden A J Blood Med. 2021; 12:581-599.

PMID: 34267570 PMC: 8275161. DOI: 10.2147/JBM.S273053.

References

Xie J, Pabon D, Jayo A, Butta N, Gonzalez-Manchon C . Type I Glanzmann thrombasthenia caused by an apparently silent beta3 mutation that results in aberrant splicing and reduced beta3 mRNA. Thromb Haemost. 2005; 93(5):897-903. DOI: 10.1160/TH04-09-0633. View

Ambo H, Kamata T, Handa M, Kawai Y, Oda A, Murata M . Novel point mutations in the alphaIIb subunit (Phe289-->Ser, Glu324-->Lys and Gln747-->Pro) causing thrombasthenic phenotypes in four Japanese patients. Br J Haematol. 1998; 102(3):829-40. DOI: 10.1046/j.1365-2141.1998.00824.x. View

Peretz H, Rosenberg N, Landau M, Usher S, Nelson E, Mor-Cohen R . Molecular diversity of Glanzmann thrombasthenia in southern India: new insights into mRNA splicing and structure-function correlations of alphaIIbbeta3 integrin (ITGA2B, ITGB3). Hum Mutat. 2006; 27(4):359-69. DOI: 10.1002/humu.20304. View

Nelson E, Nair S, Peretz H, Coller B, Seligsohn U, Chandy M . Diversity of Glanzmann thrombasthenia in southern India: 10 novel mutations identified among 15 unrelated patients. J Thromb Haemost. 2006; 4(8):1730-7. DOI: 10.1111/j.1538-7836.2006.02066.x. View

Nurden A, Pillois X, Fiore M, Alessi M, Bonduel M, Dreyfus M . Expanding the Mutation Spectrum Affecting αIIbβ3 Integrin in Glanzmann Thrombasthenia: Screening of the ITGA2B and ITGB3 Genes in a Large International Cohort. Hum Mutat. 2015; 36(5):548-61. DOI: 10.1002/humu.22776. View

Park K, Chung H, Lee K, Park I, Kim S, Kim H . Novel and recurrent mutations of ITGA2B and ITGB3 genes in Korean patients with Glanzmann thrombasthenia. Pediatr Blood Cancer. 2011; 59(2):335-8. DOI: 10.1002/pbc.24041. View

Jacquelin B, Tuleja E, Kunicki T, Nurden P, Nurden A . Analysis of platelet membrane glycoprotein polymorphisms in Glanzmann thrombasthenia showed the French gypsy mutation in the alphaIIb gene to be strongly linked to the HPA-1b polymorphism in beta3. J Thromb Haemost. 2003; 1(3):573-5. DOI: 10.1046/j.1538-7836.2003.00107.x. View

Grimaldi C, Chen F, Scudder L, Coller B, French D . A Cys374Tyr homozygous mutation of platelet glycoprotein IIIa (beta 3) in a Chinese patient with Glanzmann's thrombasthenia. Blood. 1996; 88(5):1666-75. View

George J, Caen J, Nurden A . Glanzmann's thrombasthenia: the spectrum of clinical disease. Blood. 1990; 75(7):1383-95. View

10.

Calvete J, Henschen A, Gonzalez-Rodriguez J . Complete localization of the intrachain disulphide bonds and the N-glycosylation points in the alpha-subunit of human platelet glycoprotein IIb. Biochem J. 1989; 261(2):561-8. PMC: 1138861. DOI: 10.1042/bj2610561. View

11.

Nurden A . Glanzmann thrombasthenia. Orphanet J Rare Dis. 2006; 1:10. PMC: 1475837. DOI: 10.1186/1750-1172-1-10. View

12.

Toogeh G, Sharifian R, Lak M, Safaee R, Artoni A, Peyvandi F . Presentation and pattern of symptoms in 382 patients with Glanzmann thrombasthenia in Iran. Am J Hematol. 2004; 77(2):198-9. DOI: 10.1002/ajh.20159. View

13.

Wang R, Shattil S, Ambruso D, Newman P . Truncation of the cytoplasmic domain of beta3 in a variant form of Glanzmann thrombasthenia abrogates signaling through the integrin alpha(IIb)beta3 complex. J Clin Invest. 1997; 100(9):2393-403. PMC: 508438. DOI: 10.1172/JCI119780. View

14.

Kannan M, Ahmad F, Yadav B, Kumar R, Choudhry V, Saxena R . Molecular defects in ITGA2B and ITGB3 genes in patients with Glanzmann thrombasthenia. J Thromb Haemost. 2009; 7(11):1878-85. DOI: 10.1111/j.1538-7836.2009.03579.x. View

15.

Tadokoro S, Tomiyama Y, Honda S, Arai M, Yamamoto N, Shiraga M . A Gln747-->Pro substitution in the IIb subunit is responsible for a moderate IIbbeta3 deficiency in Glanzmann thrombasthenia. Blood. 1998; 92(8):2750-8. View

16.

Nurden A, Pillois X, Nurden P . Understanding the genetic basis of Glanzmann thrombasthenia: implications for treatment. Expert Rev Hematol. 2012; 5(5):487-503. DOI: 10.1586/ehm.12.46. View

17.

Gu J, Xu W, Wang X, Wu Q, Chi C, Ruan C . Identification of a nonsense mutation at amino acid 584-arginine of platelet glycoprotein IIb in patients with type I Glanzmann thrombasthenia. Br J Haematol. 1993; 83(3):442-9. DOI: 10.1111/j.1365-2141.1993.tb04669.x. View

18.

Farsinejad A, Farajollahi M, Kazemi A, Saemi N, Faranoush M . Different biochemical expression pattern of platelet surface glycoproteins suggests molecular diversity of Glanzmann's thrombasthenia in Iran. Blood Coagul Fibrinolysis. 2013; 24(6):613-8. DOI: 10.1097/MBC.0b013e328360a558. View

19.

Nurden A . Should studies on Glanzmann thrombasthenia not be telling us more about cardiovascular disease and other major illnesses?. Blood Rev. 2017; 31(5):287-299. DOI: 10.1016/j.blre.2017.03.005. View

20.

Seligsohn U, Rososhansky S . A Glanzmann's thrombasthenia cluster among Iraqi Jews in Israel. Thromb Haemost. 1984; 52(3):230-1. View