An international, multicenter team reported in Blood that the ThromboGenomics high-throughput sequencing (HTS) test may validate recently discovered genetic variants associated with rare bleeding, thrombotic, or platelet disorders (BTPDs) in a large cohort of index patients.
In this study, samples from 2396 index patients and 156 relatives and carriers were tested using the ThromboGenomics HTS test. Clinical and laboratory phenotype information was also collected.
The overall molecular diagnostic rate was 37.3% for patients with thrombotic, coagulation, platelet count, platelet function, and unexplained bleeding.
The team identified 745 unique genetic variants, including copy number and intronic variants, approximately half of which were novel. These included 41 variants in 7 genes that were recently found to be implicated in BTPDs. In addition, 29 patients were found to have multiple variants in genes for canonical hemostasis pathways, highlighting the complex genetic underpinnings of some BTPD phenotypes.
Incidental secondary findings were reported for 4 female patients (1 patient each with likely pathogenic variants in F8 and F9 and 2 patients with a heterozygous deletion of RBM8A). The researchers noted that these variants may be actionable with respect to family planning.
The researchers concluded that “the ThromboGenomics test is a valuable addition to the diagnostic algorithm for patients with a high likelihood of having an inherited BTPD.” They added that the ThromboGenomics test may allow for “more precise prognostication and management of disease and, with cascade testing, better informed counseling of patients and their close relatives.”
1. Downes K, Megy K, Duarte D, et al. Diagnostic high-throughput sequencing of 2396 patients with bleeding, thrombotic, and platelet disorders [published online December 5, 2019]. Blood. doi:10.1182/blood.2018891192