Inherited macrothrombocytopenias comprise a heterogeneous group of inherited platelet disorders that are characterized by large platelets, thrombocytopenia and bleeding tendencies in affected individuals. Diagnostic platforms have traditionally involved a battery of complex phenotypic tests that often fail to reach a diagnosis. Next-generation sequencing lacks the pre-analytical and analytical shortcoming of these tests and provides an attractive alternate diagnostic approach. Our group has developed a candidate gene array targeting genes known to affect platelet function and tested it in a large cohort of Australasian patients with presumed platelet function disorders, particularly macrothrombocytopenia. This array identified causative variants in a significant portion of patients with uncharacterized platelet disorders, including transcription factor mutations that cannot easily be diagnosed with standard platelet phenotyping procedures. We propose that targeted genotypic screening can identify the genetic basis of platelet function defects and has the potential to be developed into a powerful clinical platform to help clinicians diagnose these rare disorders.
Part of the book: Next Generation Sequencing