1 research outputs found
Whole exome sequencing identifies genetic variants in inherited thrombocytopenia with secondary qualitative function defects
Inherited thrombocytopenias are a heterogeneous group of disorders characterised
by abnormally low platelet counts which can be associated with abnormal bleeding.
Next generation sequencing has previously been employed in these disorders for the
confirmation of suspected genetic abnormalities, and more recently in the discovery
of novel disease causing genes. However its full potential has not previously been
utilised. Over the past 6 years we have sequenced the exomes from 55 patients,
including 37 index cases and 18 additional family members, all of whom were
recruited to the UK Genotyping and Phenotyping of Platelets study. All patients had
inherited or sustained thrombocytopenia of unknown aetiology with platelet counts
varying from 11-186x109
/L. Of the 51 patients phenotypically tested, 37 (73%), had
an additional secondary qualitative platelet defect. Using whole exome sequencing
analysis we have identified “pathogenic” or “likely pathogenic” variants in 46%
(17/37) of our index patients with thrombocytopenia. In addition, we report variants
of uncertain significance in 12 index cases which include novel candidate genetic
variants in previously unreported genes in four index cases. These results
demonstrate that whole exome sequencing is an efficient method for elucidating
potential pathogenic genetic variants in inherited thrombocytopenia. Whole exome
sequencing also has the added benefit of discovering potentially pathogenic genetic
variants for further study in novel genes not previously implicated in inherited
thrombocytopenia