{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T13:50:39Z","timestamp":1792158639109,"version":"4.4.0"},"reference-count":60,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>Summary<\/jats:title>\n                  <jats:p>\n                    A heterozygous Kruppel\u2010like factor 1 (KLF1) E325K mutation causes a severe form of congenital dyserythropoietic anaemia (CDA), designated CDA\u2010IV (Online Mendelian Inheritence in Man, OMIM 613673), a rare disease with only 15 cases known. In addition to haemolytic anaemia, manifest often at birth, four of seven (57%) of 46,XY children with KLF1 E325K mutation exhibit a range of dysmorphic external genitalia including 46,XY complete sex reversal (2\/7 or 28.5%). No genital abnormalities were reported in a boy with double heterozygous\n                    <jats:italic>KLF1<\/jats:italic>\n                    null mutations, suggesting that the KLF1 E325K variant causes, in addition to its negative impacts on erythroid differentiation, disruptions in male sex differentiation. Our studies suggest a role for a cooperative effect of concurrent \u2018non\u2010pathogenic\u2019 polymorphisms in multiple genes associated with disorders of sex differentiation (DSD), notably\n                    <jats:italic>fibroblast growth factor 9<\/jats:italic>\n                    (\n                    <jats:italic>FGF9<\/jats:italic>\n                    ), whose expression was decreased in the gonads and peripheral blood in the case described here. We propose that the combined loss of FGF9 and CD44 (a target for CDA\u2010IV KLF1) resulted FGF9 signalling loss and likely caused 46,XY sex reversal. Our studies also suggest that whole\u2010blood gene expression studies in the proband\/parent triad may provide critical clues in evaluating children with DSD, the cause of which remains undiagnosed in many cases.\n                  <\/jats:p>","DOI":"10.1111\/bjh.70760","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T13:06:41Z","timestamp":1789650401000},"page":"1574-1585","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Interplay between fibroblast growth factor 9 (FGF9) and CD44 underlies 46,XY disorders of sex development in Kruppel\u2010like factor 1 (KLF\u20101)\u2010E325K\u2010associated congenital dyserythropoietic anaemia (CDA\u2010IV)"],"prefix":"10.1111","volume":"209","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9577-9624","authenticated-orcid":false,"given":"Yaddanapudi","family":"Ravindranath","sequence":"first","affiliation":[{"name":"Wayne State University School of Medicine  Detroit Michigan USA"},{"name":"Barbara Ann Karmanos Cancer Institute  Detroit Michigan USA"},{"name":"Detroit Medical Center\/Children's Hospital of Michigan  Detroit Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7917-2793","authenticated-orcid":false,"given":"Douglas B.","family":"Craig","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, University of Michigan  Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3757-3246","authenticated-orcid":false,"given":"Prahlad","family":"Parajuli","sequence":"additional","affiliation":[{"name":"Wayne State University School of Medicine  Detroit Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4978-0346","authenticated-orcid":false,"given":"Shruti","family":"Bagla","sequence":"additional","affiliation":[{"name":"Wayne State University School of Medicine  Detroit Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9439-106X","authenticated-orcid":false,"given":"Ali","family":"Saad","sequence":"additional","affiliation":[{"name":"Wayne State University School of Medicine  Detroit Michigan USA"},{"name":"Detroit Medical Center\/Children's Hospital of Michigan  Detroit Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Cukovic","sequence":"additional","affiliation":[{"name":"Wayne State University School of Medicine  Detroit Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9452-0661","authenticated-orcid":false,"given":"Markku","family":"Heikinheimo","sequence":"additional","affiliation":[{"name":"Pediatric Research Center, Children's Hospital, Helsinki University Hospital University of Helsinki  Helsinki Finland"},{"name":"Department of Pediatrics, Washington University School of Medicine St. Louis Children's Hospital  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonna","family":"Salonen","sequence":"additional","affiliation":[{"name":"Pediatric Research Center, Children's Hospital, Helsinki University Hospital University of Helsinki  Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6212-8910","authenticated-orcid":false,"given":"Katherine","family":"Regling","sequence":"additional","affiliation":[{"name":"Detroit Medical Center\/Children's Hospital of Michigan  Detroit Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0312-8750","authenticated-orcid":false,"given":"Alan","family":"Dombkowski","sequence":"additional","affiliation":[{"name":"Wayne State University School of Medicine  Detroit Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4133-7040","authenticated-orcid":false,"given":"Tony","family":"DeFalco","sequence":"additional","affiliation":[{"name":"Division of Developmental Biology, Reproductive Sciences Center Cincinnati Children's Hospital Medical Center  Cincinnati Ohio USA"},{"name":"Department of Pediatrics University of Cincinnati College of Medicine  Cincinnati Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5128-7476","authenticated-orcid":false,"given":"James J.","family":"Bieker","sequence":"additional","affiliation":[{"name":"Icahn School of Medicine at Mount Sinai  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,17]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.1991.tb04541.x"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2010.10.010"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcmd.2013.02.006"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ccr3.825"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/MPH.0000000000001042"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/MPH.0000000000001056"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.25058"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/ejh.13097"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00277-020-03982-y"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.4103\/ipcares.ipcares_43_22"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.30245"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.30955"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.31294"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-08-590968"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.beem.2009.12.002"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1002575"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/wsbm.1172"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.124.9.1653"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)00284-7"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/dez191"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/biolre\/ioaa154"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.6847"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.19128"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xpro.2021.100383"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4267"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkz501"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-09-0734"},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btr064"},{"key":"e_1_2_13_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.9471"},{"key":"e_1_2_13_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2011.08.006"},{"key":"e_1_2_13_32_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/deq167"},{"key":"e_1_2_13_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF03346683"},{"key":"e_1_2_13_34_1","doi-asserted-by":"publisher","DOI":"10.2164\/jandrol.106.000927"},{"key":"e_1_2_13_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2009.07.003"},{"key":"e_1_2_13_36_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-017-1201-0"},{"key":"e_1_2_13_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.13723"},{"key":"e_1_2_13_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41420-023-01470-6"},{"key":"e_1_2_13_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3181"},{"issue":"10","key":"e_1_2_13_40_1","first-page":"4402","article-title":"MiR\u2010665 regulates VSMCs proliferation via targeting FGF9 and MEF2D and modulating activities of Wnt\/beta\u2010catenin signaling","volume":"9","author":"Li K","year":"2017","journal-title":"Am J Transl Res"},{"key":"e_1_2_13_41_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1011606107"},{"key":"e_1_2_13_42_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddn193"},{"key":"e_1_2_13_43_1","doi-asserted-by":"publisher","DOI":"10.1159\/000522428"},{"key":"e_1_2_13_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-04918-4"},{"key":"e_1_2_13_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diff.2023.09.004"},{"key":"e_1_2_13_46_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1004996107"},{"key":"e_1_2_13_47_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M804831200"},{"key":"e_1_2_13_48_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R100043200"},{"key":"e_1_2_13_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2007.12.018"},{"key":"e_1_2_13_50_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1640-04.2004"},{"key":"e_1_2_13_51_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0177(199607)206:3<248::AID-AJA3>3.0.CO;2-I"},{"key":"e_1_2_13_52_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.112.099879"},{"key":"e_1_2_13_53_1","doi-asserted-by":"publisher","DOI":"10.1002\/iub.404"},{"key":"e_1_2_13_54_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adv1885"},{"key":"e_1_2_13_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2012.07.012"},{"key":"e_1_2_13_56_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.14261"},{"key":"e_1_2_13_57_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-020-0899-5"},{"key":"e_1_2_13_58_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020009999"},{"key":"e_1_2_13_59_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-04126-6"},{"key":"e_1_2_13_60_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.11.7964"},{"key":"e_1_2_13_61_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM197307122890205"}],"container-title":["British Journal of Haematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bjh.70760","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/bjh.70760","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bjh.70760","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T13:09:19Z","timestamp":1792156159000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bjh.70760"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,17]]},"references-count":60,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["10.1111\/bjh.70760"],"URL":"https:\/\/doi.org\/10.1111\/bjh.70760","archive":["Portico"],"relation":{},"ISSN":["0007-1048","1365-2141"],"issn-type":[{"value":"0007-1048","type":"print"},{"value":"1365-2141","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,17]]},"assertion":[{"value":"2026-04-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-15","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-17","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}