z-logo
Premium
Whole exome sequencing in the diagnostic workup of patients with a bleeding diathesis
Author(s) -
Saes Joline L.,
Simons Annet,
de Munnik Sonja A.,
Nijziel Marten R.,
Blijlevens Nicole M. A.,
Jongmans Marjolijn C.,
van der Reijden Bert A.,
Smit Yolba,
Brons Paul P.,
van Heerde Waander L.,
Schols Saskia E. M.
Publication year - 2019
Publication title -
haemophilia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.213
H-Index - 92
eISSN - 1365-2516
pISSN - 1351-8216
DOI - 10.1111/hae.13638
Subject(s) - exome sequencing , bleeding diathesis , medicine , platelet disorder , exome , omim : online mendelian inheritance in man , diathesis , mendelian inheritance , genetic testing , candidate gene , phenotype , genetic analysis , bioinformatics , gene , genetics , platelet , immunology , biology
Bleeding assessment tools and laboratory phenotyping often remain inconclusive in patients with a haemorrhagic diathesis. Aim To describe the phenotype and genetic profile of patients with a bleeding tendency. Methods Whole exome sequencing (WES) was incorporated in the routine diagnostic pathway of patients with thrombocytopenia (n = 17), platelet function disorders (n = 19) and an unexplained bleeding tendency (n = 51). The analysis of a panel of 126 OMIM (Online Mendelian Inheritance in Man) genes involved in thrombosis and haemostasis was conducted, and if negative, further exome‐wide analysis was performed if informed consent given. Results Eighteen variants were detected in 15 patients from a total of 87 patients (17%). Causative variants were observed in MYH9 (two cases), SLFN14 , P2RY12 and GP9. In addition, one case was considered solved due to combined carriership of F7 and F13A1 variants and one with combined carriership of F2 , F8 and VWF , all variants related to secondary haemostasis protein aberrations. Two variants of uncertain significance (VUS) were found in two primary haemostasis genes: GFI1B and VWF . Eight patients were carriers of autosomal recessive disorders . Exome‐wide analysis was performed in 54 cases and identified three variants in candidate genes. Conclusion Based on our findings, we conclude that performing WES at the end of the diagnostic trajectory can be of additive value to explain the complete bleeding phenotype in patients without a definite diagnosis after conventional laboratory tests. Discovery of combinations of (novel) genes that predispose to bleeding will increase the diagnostic yield in patients with an unexplained bleeding diathesis.

This content is not available in your region!

Continue researching here.

Having issues? You can contact us here