APPLICATION OF WHOLE EXOME SEQUENCING FOR PATIENTS WITH INHERITED PLATELET DISORDERS
Author(s): ,
Marian Stevens-Kroef
Affiliations:
Radboud university medical center,Nijmegen,Netherlands
,
Sonja de Munnik
Affiliations:
Radboud university medical center,Nijmegen,Netherlands
,
Waander van Heerde
Affiliations:
Radboud university medical center,Nijmegen,Netherlands
,
Paul Brons
Affiliations:
Radboud university medical center,Nijmegen,Netherlands
,
Joline Saes
Affiliations:
Radboud university medical center,Nijmegen,Netherlands
,
Saskia Schols
Affiliations:
Radboud university medical center,Nijmegen,Netherlands
Annet Simons
Affiliations:
Radboud university medical center,Nijmegen,Netherlands
EHA Library. Stevens-Kroef M. Jun 15, 2019; 267093; PS1476
Dr. Marian Stevens-Kroef
Dr. Marian Stevens-Kroef
Contributions
Abstract

Abstract: PS1476

Type: Poster Presentation

Presentation during EHA24: On Saturday, June 15, 2019 from 17:30 - 19:00

Location: Poster area

Background
Inherited platelet disorders (IPDs) are disorders consisting of thrombocytopenia, thromobocytopathy or a combination of these. Diagnosis is often hampered by the lack of specificity and correct validation of current hematological assays. In addition, these disorders exhibit a genetic heterogeneity with over 50 genes involved.

Aims
This study evaluates an upfront diagnostic strategy using whole-exome sequencing (WES) with a targeted analysis of a panel of 145 genes involved in thrombosis and hemostasis in patients suspected for an IPD.

Methods
Sixty-Six patients suspicious for an IPD were subjected to WES, followed by targeted analysis of 145 genes (besides platelet genes also genes involved in coagulation and venous thrombosis embolism are analyzed). Variants were classified according to the five-tier (class 1 to class 5) scheme.

Results
Fourteen patients (21%) harbored (likely) pathogenic variants that explained the clinical spectrum in these patients. Genes affected in these patients were GP9, MYH9 (2 cases), NBEAL2, P2RY12, RUNX1 (3 cases),  SLFN14  and VWF (2 cases), all these genes are involved in thrombocytopenia or thromobocytopathy.  In the disorders with an autosomal recessive mode of inheritance either the mutation was homozygous (GP9 and P2RY12), or compound heterozygous (NBEAL2). Additionally, 2 patients with a mutation in the THPO gene and 1 patient with a mutation in SEPRINC1  were observed, both genes are known to be involved in venous thrombosis.

In  4 (6%) other patients only one heterozygous  (likely) pathogenic variant of an autosomal recessive disease gene was observed. In 12 patients (18%) a variant of unknown significance (VUS/class 3) was observed. Further segregation studies within the family and functional studies are required to fully solve these cases.

Conclusion
We found that WES is a powerful tool in genetically diagnosing patients with IPD.

Session topic: 32. Platelets disorders

Keyword(s): Diagnosis, Inherited platelet disorders

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