Three novel mutations in the glycoprotein IIb gene in a patient with type II Glanzmann thrombasthenia

Area of Science:

• Hematology
• Molecular Biology
• Genetics

Background:

• Glanzmann thrombasthenia is a rare inherited bleeding disorder characterized by defective platelet aggregation.
• Platelet glycoproteins (GP) IIb/IIIa play a crucial role in the final common pathway of platelet aggregation.
• Reduced levels of GP IIb/IIIa are a hallmark of type II Glanzmann thrombasthenia.

Observation:

• A patient with type II Glanzmann thrombasthenia exhibited significantly reduced levels of GP IIb and IIIa in their platelets.
• Three novel mutations were identified in the gene encoding GP IIb (GPIIb): c.440C->G/p.Leu116Val, c.1772_1773insG/p.Asp560GlyfsX16, and c.2438C->A/p.His782Asn.

Findings:

• The mutation p.Leu116Val was determined not to be causative.
• The c.1772_1773insG mutation led to an early stop codon, resulting in non-sense mediated decay of mRNA and a truncated protein unable to complex with GPIIIa.
• The p.His782Asn mutation impaired the proper transport and maturation of the pro-GPIIb/IIIa complex within the cell, preventing its surface expression.

Implications:

• These findings elucidate the molecular mechanisms underlying GP IIb/IIIa deficiency in this patient.
• Understanding these novel mutations provides insights into the structure-function relationship of GP IIb and its role in platelet formation.
• This genetic information can aid in the diagnosis and potential future therapeutic strategies for Glanzmann thrombasthenia.