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No known genetic etiologies for neutropenia or bone marrow failure were found. However, next\u2010generation sequencing of germline samples from the patient revealed a novel, de novo germline stop\u2010loss mutation in the X\u2010linked gene <jats:italic>SEPT6<\/jats:italic> that resulted in reduced SEPT6 staining in bone marrow granulocyte precursors and megakaryocytes. Patient skin fibroblast\u2010derived induced pluripotent stem cells (iPSCs) produced reduced myeloid colonies, particularly of the granulocyte lineage. CRISPR\/Cas9 knock\u2010in of the patient's mutation or complete knock\u2010out of <jats:italic>SEPT6<\/jats:italic> was not tolerated in non\u2010patient\u2010derived iPSCs or human myeloid cell lines, but <jats:italic>SEPT6<\/jats:italic> knock\u2010out was successful in an erythroid cell line and resulting clones revealed a propensity to multinucleation. In silico analysis predicts that the mutated protein hinders the dimerization of SEPT6 coiled\u2010coils in both parallel and antiparallel arrangements, which could in turn impair filament formation. These data demonstrate a critical role for <jats:italic>SEPT6<\/jats:italic> in chromosomal segregation in myeloid progenitors that can account for the unusual predisposition to aneuploidy and dysmyelopoiesis.<\/jats:p>","DOI":"10.1002\/ajh.26382","type":"journal-article","created":{"date-parts":[[2021,10,22]],"date-time":"2021-10-22T14:36:12Z","timestamp":1634913372000},"page":"18-29","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Congenital X\u2010linked neutropenia with myelodysplasia and somatic tetraploidy due to a germline mutation in <scp>SEPT6<\/scp>"],"prefix":"10.1002","volume":"97","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5041-2308","authenticated-orcid":false,"given":"Raffaele","family":"Renella","sequence":"first","affiliation":[{"name":"Pediatric Hematology\u2010Oncology Research Laboratory Lausanne University Hospital  Switzerland"},{"name":"Division of Hematology\u2010Oncology Boston 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