{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:43:54Z","timestamp":1787028234713,"version":"build-2736575974"},"reference-count":32,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,5,11]],"date-time":"2023-05-11T00:00:00Z","timestamp":1683763200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>The discovery in 2005 of the JAK2 V617F gain-of-function mutation in myeloproliferative neoplasms and more particularly in polycythemia vera has deeply changed the diagnostic and therapeutic approaches to polycythemia. More recently, the use of NGS in routine practice has revealed a large number of variants, although it is not always possible to classify them as pathogenic. This is notably the case for the JAK2 E846D variant for which for which questions remain unanswered. In a large French national cohort of 650 patients with well-characterized erythrocytosis, an isolated germline heterozygous JAK2 E846D substitution was observed in only two cases. For one of the patients, a family study could be performed, without segregation of the variant with the erythrocytosis phenotype. On the other hand, based on the large UK Biobank resource cohort including more than half a million UK participants, the JAK2 E846D variant was found in 760 individuals, associated with a moderate increase in hemoglobin and hematocrit values, but with no significant difference to the mean values of the rest of the studied population. Altogether, our data as well as UK Biobank cohort analyses suggest that the occurrence of an absolute polycythemia cannot be attributed to the sole demonstration of an isolated JAK2 E846D variant. However, it must be accompanied by other stimuli or favoring factors in order to generate absolute erythrocytosis.<\/jats:p>","DOI":"10.3390\/genes14051066","type":"journal-article","created":{"date-parts":[[2023,5,12]],"date-time":"2023-05-12T01:05:10Z","timestamp":1683853510000},"page":"1066","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Germline JAK2 E846D Substitution as the Cause of Erythrocytosis?"],"prefix":"10.3390","volume":"14","author":[{"given":"Nada","family":"Maaziz","sequence":"first","affiliation":[{"name":"Laboratoire de G\u00e9n\u00e9tique Chromosomique et Mol\u00e9culaire, P\u00f4le Biologie, CHU de Dijon, 21000 Dijon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9line","family":"Garrec","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique M\u00e9dicale, CHU de Nantes, 44000 Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrice","family":"Airaud","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique M\u00e9dicale, CHU de Nantes, 44000 Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Bob\u00e9e","sequence":"additional","affiliation":[{"name":"Service d\u2019H\u00e9matologie Biologique, CHU de Rouen, 76000 Rouen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Contentin","sequence":"additional","affiliation":[{"name":"Service d\u2019H\u00e9matologie, Centre Henri Becquerel, 76000 Rouen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilie","family":"Cayssials","sequence":"additional","affiliation":[{"name":"Service d\u2019Oncologie H\u00e9matologique, CHU de Poitiers, 86000 Poitiers, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2971-4926","authenticated-orcid":false,"given":"Antoine","family":"Rimbert","sequence":"additional","affiliation":[{"name":"l\u2019Institut du Thorax, INSERM, Nantes Universit\u00e9, CHU Nantes, 44300 Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard","family":"Aral","sequence":"additional","affiliation":[{"name":"Laboratoire de G\u00e9n\u00e9tique Chromosomique et Mol\u00e9culaire, P\u00f4le Biologie, CHU de Dijon, 21000 Dijon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0095-1319","authenticated-orcid":false,"given":"St\u00e9phane","family":"B\u00e9zieau","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique M\u00e9dicale, CHU de Nantes, 44000 Nantes, France"},{"name":"l\u2019Institut du Thorax, INSERM, Nantes Universit\u00e9, CHU Nantes, 44300 Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Betty","family":"Gardie","sequence":"additional","affiliation":[{"name":"l\u2019Institut du Thorax, INSERM, Nantes Universit\u00e9, CHU Nantes, 44300 Nantes, France"},{"name":"Ecole Pratique des Hautes Etudes, Universit\u00e9 PSL, 75006 Paris, France"},{"name":"Laboratory of Excellence GR-Ex, Imagine Institute, 75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3151-1068","authenticated-orcid":false,"given":"Fran\u00e7ois","family":"Girodon","sequence":"additional","affiliation":[{"name":"Laboratory of Excellence GR-Ex, Imagine Institute, 75015 Paris, France"},{"name":"Service d\u2019H\u00e9matologie Biologique, P\u00f4le Biologie, CHU de Dijon, 21000 Dijon, France"},{"name":"Inserm U1231, Universit\u00e9 de Bourgogne, 21000 Dijon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1111\/j.1365-2141.2005.05517.x","article-title":"An elevated venous haemoglobin concentration cannot be used as a surrogate marker for absolute erythrocytosis: A study of patients with polycythaemia vera and apparent polycythaemia","volume":"129","author":"Johansson","year":"2005","journal-title":"Br. 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