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Clinical and molecular diagnosis of hereditary and idiopathic erythrocytosis Volume 28, issue 1, Janvier-Février 2022

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Authors
1 École pratique des hautes études (EPHE), université Paris Sciences et Lettres, France
2 Université de Nantes, CNRS, INSERM, l’institut du thorax, Nantes, France
3 Laboratoire d’Excellence GR-Ex
4 Laboratoire de génétique chromosomique et moléculaire, pôle biologie, CHU de Dijon, Dijon, France
5 Service d’hématologie biologique, pôle biologie, CHU de Dijon, Dijon, France
6 Inserm U1231, université de Bourgogne, Dijon, France
7 Intergroupe des syndromes myéloprolifératifs français (FIM)
* Tirés à part

Erythrocytosis is defined by an increased red cell mass measured by an isotope method. The best characterized erythrocytosis is Polycythaemia Vera (PV), a myeloproliferative neoplasm caused by an acquired mutation of the JAK2 gene (JAK2-V617F mutation in more than 95 % of cases). However, other types of erythrocytosis exist and are of major importance. They can be either hereditary (hereditary erythrocytosis - HE) or diagnosed in adult patients without any family history (idiopathic erythrocytosis - IE). HE/IE are not related to myeloproliferative disorder but may be associated with severe thromboembolic events, pulmonary hypertension and, occasionally, tumors. HE/IE are rare conditions, usually diagnosed after extensive testing, including molecular genetic testing. A family history of erythrocytosis is highly suggestive of HE, but is often unrecognized or unnoticed in less symptomatic forms. Consequently, the diagnosis of HE is frequently established in adulthood, sometimes late in life. The use of next generation sequencing methods allows in the vast majority of cases to specify the molecular cause. Nevertheless, these methods only elucidate the origin of erythrocytosis classified as idiopathic in one out of four cases, which encourages further research in this field. We report here the different genomic abnormalities related to hereditary erythrocytosis, the new discoveries regarding the main involved genes (EPOR, VHL, PHD2, HIF2A, EPO, etc.) and propose some guidelines in the diagnostic approach and the therapeutic management.