Abstract Number: PB0359
Meeting: ISTH 2021 Congress
Background: Inherited bleeding and thrombotic disorders are a heterogeneous group caused by DNA variants in a large number of loci. Their actual incidence is unknown because most of them are infra or misdiagnosed. Next generation sequencing (NGS) has provided information about diagnosis that impact on clinical management.
Aims: We are using NGS since 2019 and we show our findings below.
Methods: Our custom-gene panel (Nonacus) included 83 genes: 32 associated to bleeding disorders, 20 to thrombosis and 31 to platelet disorders (table 1). Genes were selected according to previous evidence supporting their potential role in these pathologies. The sequencing results were processed by using a bioinformatic approach (Data genomics, Imegen) and assessed following the ACMG Guidelines.
Results: Ninety-seven patients were studied. We identified 50 mutations in 50 patients in 30 different genes: 13 (26%) were pathogenic, 11 (22%) probably pathogenic, 1 (2%) probably benign, 14 (28%) benign and 11 (22%) mutations with unknown significance (table 2). Considering pathogenic and probably pathogenic mutations, molecular diagnosis was established in 24 (48%) patients.
In 20 out of 30 cases there was a prior clinical suspicion due to phenotypic conventional findings. But mutations in the HPS1, NBEAL, TUBB1, and SERPINE1 genes detected by NGS were very helpful in diagnosis.
Conclusions: A good phenotypic characterization is important in order to offer appropriate molecular diagnosis with custom-gene-panels. In some cases, NGS is the only diagnosis tool.
By using NGS we found a high proportion (22%) of mutations with unknown significance. To characterize their role in diseases, it would be necessary to perform functional studies.
A conclusive molecular diagnosis may impact clinical management.
To cite this abstract in AMA style:Vilalta N, Tirado I, Romero L, Millón JA, Carrasco M, Corrochano M, Souto JC, Mateo J. Next Generation Sequencing in Patients with Bleeding, Thrombotic and Platelet Disorders: A Single Centre Experience [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/next-generation-sequencing-in-patients-with-bleeding-thrombotic-and-platelet-disorders-a-single-centre-experience/. Accessed December 2, 2022.
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