**DNA-based Diagnosis of Uncharacterized Inherited Macrothrombocytopenias Using Next-generation Sequencing Technology with a Candidate Gene Array**

David J. Rabbolini, Marie-Christine Morel Kopp, Sara Gabrielli, Qiang Chen, William S. Stevenson and Christopher M. Ward

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/61777

#### **Abstract**

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386 Next Generation Sequencing - Advances, Applications and Challenges

Inherited macrothrombocytopenias comprise a heterogeneous group of inherited platelet disorders that are characterized by large platelets, thrombocytopenia and bleeding ten‐ dencies in affected individuals. Diagnostic platforms have traditionally involved a bat‐ tery 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 pro‐ vides 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 macro‐ thrombocytopenia. This array identified causative variants in a significant portion of pa‐ tients with uncharacterized platelet disorders, including transcription factor mutations that cannot easily be diagnosed with standard platelet phenotyping procedures. We pro‐ pose 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.

**Keywords:** Inherited macrothrombocytopenia, next-generation sequencing, candidate gene array
