{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T15:10:37Z","timestamp":1789139437145,"version":"build-2803163510"},"reference-count":18,"publisher":"BMJ","issue":"8","license":[{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"unspecified","delay-in-days":11,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Case Rep"],"accepted":{"date-parts":[[2026,7,28]]},"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:p>\n                    Familial erythrocytosis is a rare disorder most often linked to germline alterations affecting erythropoiesis and oxygen-sensing pathways. The\n                    <jats:italic>EGLN1<\/jats:italic>\n                    gene encodes prolyl hydroxylase domain-containing protein 2 (PHD2), a central regulator of the hypoxia-inducible factor (HIF) pathway that modulates erythropoietin (EPO) production. This report describes a mother and son with longstanding erythrocytosis, both harbouring a heterozygous\n                    <jats:italic>EGLN1<\/jats:italic>\n                    variant of uncertain significance (c.806T&gt;C, p.Ile269Thr), in whom secondary causes and\n                    <jats:italic>JAK2<\/jats:italic>\n                    -mutated myeloproliferative neoplasms were excluded. Both individuals required serial phlebotomy for haematocrit control and biochemical as well as molecular testing supported congenital erythrocytosis. The\n                    <jats:italic>EGLN1<\/jats:italic>\n                    variant has been reported rarely and is supported by in-silico and functional data suggesting deleterious effects on PHD2 protein stability and function. Based on the aggregate evidence derived from a European cohort, this variant has previously been proposed to meet the criteria for pathogenic classification under the ACMG guidelines. This case adds clinical and functional evidence supporting ACMG\/AMP-based classification of\n                    <jats:italic>EGLN1<\/jats:italic>\n                    c.806T&gt;C (p.Ile269Thr) as likely pathogenic in familial erythrocytosis.\n                  <\/jats:p>","DOI":"10.1136\/bcr-2026-272167","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T12:40:36Z","timestamp":1786538436000},"page":"e272167","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Familial erythrocytosis associated with an\n                    <i>EGLN1<\/i>\n                    (PHD2) variant of uncertain significance with emerging evidence of pathogenicity"],"prefix":"10.1136","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0565-8752","authenticated-orcid":false,"given":"Anil","family":"Ananthaneni","sequence":"first","affiliation":[{"name":"Hematology\/Oncology, Louisiana State University Health Sciences Center Shreveport, Shreveport, Louisiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-0686-7461","authenticated-orcid":false,"given":"Kirsten","family":"Maddox","sequence":"additional","affiliation":[{"name":"School of Medicine, Louisiana State University Health Sciences Center Shreveport, Shreveport, Louisiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7270-3720","authenticated-orcid":false,"given":"Riya","family":"Sam","sequence":"additional","affiliation":[{"name":"Internal Medicine, Advocate Illinois Masonic Medical Center Advocate Library Network, Chicago, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7547-2315","authenticated-orcid":false,"given":"Poornima","family":"Ramadas","sequence":"additional","affiliation":[{"name":"Louisiana State University Health Sciences Center Shreveport, Shreveport, Louisiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2026,8,12]]},"reference":[{"key":"2026091107251250000_19.8.e272167.1","doi-asserted-by":"publisher","DOI":"10.1182\/asheducation-2009.1.629"},{"key":"2026091107251250000_19.8.e272167.2","doi-asserted-by":"publisher","DOI":"10.2147\/HP.S54455"},{"key":"2026091107251250000_19.8.e272167.3","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2018-06-854711"},{"key":"2026091107251250000_19.8.e272167.4","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1002\/ccr3.1499","article-title":"Congenital erythrocytosis - discover of a new mutation in the EGLN1 gene","volume":"6","author":"Barradas","year":"2018","journal-title":"Clin Case Rep"},{"key":"2026091107251250000_19.8.e272167.5","doi-asserted-by":"crossref","first-page":"232","DOI":"10.7150\/ijms.4.232","article-title":"Familial Polycythemia Caused by a Novel Mutation in the Beta Globin Gene: Essential Role of P50 in Evaluation of Familial Polycythemia","volume":"4","author":"Agarwal","year":"2007","journal-title":"Int J Med Sci"},{"key":"2026091107251250000_19.8.e272167.6","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22448"},{"key":"2026091107251250000_19.8.e272167.7","first-page":"518","article-title":"Erythrocytosis: genes and pathways involved in disease development","volume":"19","author":"Ga\u0161per\u0161i\u010d","year":"2021","journal-title":"Blood Transfus"},{"key":"2026091107251250000_19.8.e272167.8","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2009.54"},{"key":"2026091107251250000_19.8.e272167.9","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1002\/ajh.26920","article-title":"JAK2 unmutated erythrocytosis: 2023 Update on diagnosis and management","volume":"98","author":"Gangat","year":"2023","journal-title":"Am J Hematol"},{"key":"2026091107251250000_19.8.e272167.10","doi-asserted-by":"crossref","first-page":"1965","DOI":"10.1007\/s00277-021-04546-4","article-title":"Diagnosis and management of non-clonal erythrocytosis remains challenging: a single centre clinical experience","volume":"100","author":"An\u017eej Doma","year":"2021","journal-title":"Ann Hematol"},{"key":"2026091107251250000_19.8.e272167.11","doi-asserted-by":"crossref","unstructured":"Oliveira JL , Coon LM , Frederick LA , et al . Genotype-Phenotype Correlation of Hereditary Erythrocytosis Mutations, a single center experience. 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