Abstract Number: OC 04.1
Meeting: ISTH 2021 Congress
Background: High-throughput sequencing (HTS) has revolutionized the molecular diagnosis of Inherited platelet disorders (IPDs). We have implemented a target gene sequencing (TGS) panel in the routine clinical practice since 2016.
Aims: To evaluate the applicability of the TGS panel for the molecular approach in the diagnosis of IPDs in the clinical practice.
Methods: We performed a prospective study of 254 index patients, enrolled in the multicenter Spanish Project in IPDs. Patients were presumed to carry IPDs by specific phenotypes (high suspicious of candidate genes) or had uncertain phenotypes (no candidate genes) (Table 1 and Figure 1). Informed consent was obtained and the study was approved by a recognized medical ethics committee.
Results: A molecular diagnosis was achieved in 160 patients (63%). More patients with specific phenotypes reached a diagnosis (91%) than those with unspecific manifestations (53%) (Figure 1). We confirmed the molecular in all cases with inherited thrombocytopenia (IT) and specific phenotypes, especially in MYH9-RD, Bernard Soulier syndrome and FPD/LMA. The percentage was 81% in inherited platelet function disorders (IPFD) with specific phenotypes (Glanzmann thrombasthenia, and dense granules disorders). In individuals with unspecific manifestations, more genetics variants were found in patients with IT (57%, mainly TUBB1-RT, mBSS, and ITGA2B/ITGB3-RT), than in those with IPFD (34%) (Figure 1). Very rare disorders were identified (SRC-RT, TPM4-RT, MECOM-RT, GATA1-RT, sitosterolemia, or COX1-RD). We found 161 different candidate variants (PV:36%; LPV:44% and VUS:19%) in 45 genes, according to ACGM guidelines. Most of them were missense/nonsense (78%). Seventy variants (44%) were novel.
Main features of inclued patients in the study | Total |
Patients included (%):
|
254 (100)
68 (26) |
Median age (range) | 30 years (0 – 92) |
Females (%) | 148 (58) |
Median Bleeding Score (range) | 3 (0-35) |
Median platelet count (range) | 90×109/L (2 – 617) |
Family history (%) | 157 (63%) |
Type of IPD:
|
62 (24) 192 (76) 3 (1) 50 (20) 139 (55) |
Impaired aggregation responses (%) | 105 (41) |
Achieved molecular diagnosis (%) | 160 (63) |
Conclusions: Our study reinforces the feasibility of applying our TGS panel in the clinical practice mainly in specific IPDs. It has proven to be (1) very useful in IT with specific phenotypes, (2) somewhat useful in IT with unspecific manifestations, and also to identify some rare disorders, and (3) not too useful to diagnose IPFDs with unspecific phenotypes.
To cite this abstract in AMA style:
Bastida JM, L Lozano M, Benito R, Rodríguez-Alén A, Butta N, Fernández-Mosteirin: N, Sevivas T, Marco-Rico A, Revilla N, Huertas-Aragonés J, Marin-Quílez A, Palma-Barqueros V, Marcellini S, Velasco P, Nieto MdM, Sierra-Aisa C, Alonso MN, F López-Fernández M, González-Porras: JR, Rivera J, GEAPC Study Group . High Throughput Sequencing for the Molecular Diagnosis of Inherited Platelet Disorders in Spain. Experience of the GEAPC Group [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/high-throughput-sequencing-for-the-molecular-diagnosis-of-inherited-platelet-disorders-in-spain-experience-of-the-geapc-group/. Accessed March 22, 2024.« Back to ISTH 2021 Congress
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