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However, anaemia caused by <jats:italic>EPAS1<\/jats:italic> loss\u2010of\u2010function mutations has been confined to only one case report, and the underlying mechanism remains unclear. Herein, the reanalysis of high\u2010throughput sequencing data from 311 patients with anaemia identified three monoallelic <jats:italic>EPAS1<\/jats:italic> variants from three unrelated families in a paediatric anaemia cohort. The probands showed highly consistent clinical phenotypes with normocytic and normochromic anaemia, reticulocytopenia and relative deficiency of serum EPO, characterised as congenital hypoplastic anaemia. In\u00a0vitro studies suggested that defects in steady\u2010state protein abundance, nuclear localisation and binding with co\u2010activator in <jats:italic>EPAS1<\/jats:italic> variants lead to impaired <jats:italic>EPO<\/jats:italic> transcriptional activation. Therefore, loss\u2010of\u2010function mutations in <jats:italic>EPAS1<\/jats:italic> can cause erythroid hypoplasia in an EPO\u2010dependent manner. This study identified a new causative gene for congenital hypoplastic anaemia and clarified the molecular aetiology of loss\u2010of\u2010function <jats:italic>EPAS1<\/jats:italic> mutations.<\/jats:p>","DOI":"10.1111\/bjh.19930","type":"journal-article","created":{"date-parts":[[2024,11,30]],"date-time":"2024-11-30T01:59:34Z","timestamp":1732931974000},"page":"585-595","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Elucidating loss\u2010of\u2010function mechanisms of monoallelic <scp><i>EPAS1<\/i><\/scp> mutations underlying congenital hypoplastic anaemia in a paediatric anaemia cohort"],"prefix":"10.1111","volume":"206","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5578-2463","authenticated-orcid":false,"given":"Jiasheng","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Medical Genetics and Molecular Diagnostic Laboratory, Shanghai Children's Medical Center Shanghai Jiao Tong 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