Congenital macrothrombocytopenia is a heterogeneous disorder in India.

Introduction Inherited macrothrombocytopenia represents a heterogeneous group of disorders which are characterized by the presence of a reduced number of abnormally large platelets in the circulation, which may or may not be associated with a bleeding tendency. In spite of several causative genes having been identified, the underlying genetic defects remain to be identified in approximately half of the cases. Aims To understand the molecular pathology of isolated giant platelet disorder from India. Materials and methods We studied 112 cases that were referred for investigation of macrothrombocytopenia. Agonist induced platelet aggregation and platelet GP1b/ IX/V receptor expression were investigated to assess GP1b/ IX/V receptor expression and the GP1 BA, GP1 BB, GP9, ABCG5, ABCG8, TUBB1 and MYH9 genes were analysed to identify candidate gene defects. Results Twenty-three candidate gene defects were identified in 48 of 112 cases, 20 of which were novel. Of the candidate defects identified, 91% were missense and 9% were nonsense variations. The missense variations were in GP9 (9), ABCG5 (4), GP1 BB (3), GP1 BA (3) and MYH9 (2), while the nonsense defects occurred in MYH9 (1) and GP1 BA (1). Conclusions This study increases the understanding of the molecular basis of an isolated giant platelet disorder, a common heterogeneous condition prevalent in north and eastern India. [ABSTRACT FROM AUTHOR]