A high-throughput sequencing test for diagnosing inherited bleeding, thrombotic, and platelet disorders

Abstract

Key Points Developed a targeted sequencing platform covering 63 genes linked to heritable bleeding, thrombotic, and platelet disorders. The ThromboGenomics platform provides a sensitive genetic test to obtain molecular diagnoses in patients with a suspected etiology.

A comprehensive targeted next‐generation sequencing panel for genetic diagnosis of patients with suspected inherited thrombocytopenia

“…This detection rate is in keeping with other recent previous large‐scale targeted panel sequencing studies and the application of WES to patients with IT of unknown etiology 4 , 12 , 20 , 21 . One possible explanation for the inflated detection rate for panel based platforms is the relative increase in average read coverage when compared to WES analysis, especially at the point of variation.…”

Application of whole‐exome sequencing to direct the specific functional testing and diagnosis of rare inherited bleeding disorders in patients from the Öresund Region, Scandinavia

“…This approach was made possible due to a pre ‐ established in‐house genomic centre and an existing close collaboration between the two coagulation units localized in the Öresund Region. To date, in the diagnostic work‐up of rare IBD, NGS‐based gene panels have been implemented by two large research collaborations: the ThromboGenomics platform (Simeoni et al , 2016) and the GAPP study group (Johnson et al , 2016). We implemented WES in our clinics, allowing consecutive expansion of the number of genes analysed.…”

“…Of particular interest, only one of our patients had a (benign) variant in the gene ( P4HB ) encoding PDI, indicating that PDI variants were not a common cause of bleeding disorders in our patient cohort. We anticipate that an additional number of our patients will be diagnosed by WES, especially those patients with a normal platelet count, given the considerable efforts that are currently being directed towards the discovery of new causal variants in IBD patients (Bariana et al , 2017; Johnson et al , 2016; Simeoni et al , 2016). …”

“…A remarkable effort has been made by the ThromboGenomics consortium that has designed an next generation sequencing (NGS)‐based panel targeting 63 genes relevant for inherited bleeding and thrombotic disorders, allowing for a molecular diagnosis in cases where an IBD or thrombotic disorder is suspected on laboratory or clinical findings (Simeoni et al , 2016). Another approach has been taken by the UK Genotyping and Phenotyping of Platelets (GAPP) study that enrols patients with increased bleeding tendency of unknown aetiology.…”

Preoperative Detection of Low Von Willebrand Factor Activity and Operative Blood Loss in Pediatric Scoliosis Patients Undergoing Posterior Spinal Fusion

“…In the next decade, our understanding of inherited bleeding disorders and the appropriate use of pro-coagulant therapy will evolve as high throughput gene sequencing tests are being developed to assess bleeding disorders in a highly specific manner [27]. Indeed there are new genomic loci for VWD being determined and our understanding of the downstream disruption of the coagulation pathway from having a low VWF: RCo levels will become better characterized and even potentially personalized [28].…”