Exome sequencing in 116 patients with inherited thrombocytopenia that remained of unknown origin after systematic phenotype-driven diagnostic workup.

Inherited thrombocytopenias (IT) are genetic diseases characterized by low platelet count, sometimes associated with congenital defects or a predisposition to develop additional conditions. Next-generation sequencing has substantially improved our knowledge of IT, with more than 40 genes identified so far, but obtaining a molecular diagnosis remains a challenge especially for patients with non-syndromic forms, having no clinical or functional phenotypes that raise suspicion about specific genes. We performed exome sequencing (ES) in a cohort of 116 IT patients (89 families), still undiagnosed after a previously validated phenotype-driven diagnostic algorithm including a targeted analysis of suspected genes.

Treatment of inherited thrombocytopenias.

The new techniques of genetic analysis have made it possible to identify many new forms of inherited thrombocytopenias (IT) and study large series of patients. In recent years, this has changed the view of IT, highlighting the fact that, in contrast to previous belief, most patients have a modest bleeding diathesis. On the other hand, it has become evident that some of the mutations responsible for platelet deficiency predispose the patient to serious, potentially lifethreatening diseases.