title: Inherited disorders of platelet function: selected updates.
abstract: The gene variants responsible for the primary genotype of many platelet disorders have now been identified. Next-generation sequencing technology (NGST), mainly exome sequencing, has highlighted genes responsible for defects in platelet secretion (NBEAL2, gray platelet syndrome), procoagulant activity (STIM1, Stormorken syndrome), and activation pathways (RASGRP2, CalDAG-GEFI deficiency and integrin dysfunction; PRKACG, cyclic adenosine monophosphate-dependent protein kinase deficiency). Often disorders of platelet function are associated with a modified platelet production with changes in platelet number and size and can accompany malfunction of other organs or tissues. Most families have private mutations, and gene variants may prevent protein synthesis, abrogate function, or result in aberrant activated proteins. Nevertheless, bleeding severity is difficult to predict by genotype alone suggesting other factors. A major new challenge of NGST is to identify these factors and help improve patient care. This review concentrates on recent developments and is illustrated from personal observations.
authors.affiliation: Institut de Rhythmologie et de Modélisation Cardiaque, Plateforme Technologique d'Innovation Biomédicale, Hôpital Xavier Arnozan, Pessac, France.
authors.forename: A T
authors.initials: AT
authors.lastname: Nurden
authors.affiliation: Institut de Rhythmologie et de Modélisation Cardiaque, Plateforme Technologique d'Innovation Biomédicale, Hôpital Xavier Arnozan, Pessac, France.
authors.forename: P
authors.initials: P
authors.lastname: Nurden
mesh_terms: D000818:Animals; D001791:Blood Platelet Disorders / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D001792:Blood Platelets / Q000378:metabolism*; D004252:DNA Mutational Analysis / Q000379:methods; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006470:Hemorrhage / Q000235:genetics*; D006487:Hemostasis / Q000235:genetics*; D040941:Heredity; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D009154:Mutation; D010641:Phenotype; D012307:Risk Factors; D015398:Signal Transduction
chemical_list: D005819:Genetic Markers
keywords: Glanzmann thrombasthenia; blood platelets; genetic variation; hemorrhage; high‐throughput nucleotide sequencing; rare diseases