{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T08:02:41Z","timestamp":1779782561139,"version":"3.53.1"},"reference-count":7,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T00:00:00Z","timestamp":1769472000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T00:00:00Z","timestamp":1769472000000},"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":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Hypotrichosis\u2010lymphedema\u2010telangiectasia syndrome (HLTS) is a congenital disorder characterized by lymphedema, telangiectasia, and hypotrichosis or alopecia, caused by mutations in the SRY\u2010related high\u2010mobility group box (\n                    <jats:italic>SOX<\/jats:italic>\n                    ) 18 gene. We report the case of a 10\u2010year\u2010old boy who presented with aortic valve regurgitation, marbled skin, minor anomalies, and iron\u2010deficiency anemia due to frequent mucosal bleeding. At 5\u2009years of age, he experienced significant hemostatic difficulties following the extraction of a deciduous tooth. The usual doses of iron supplementation did not cure his iron\u2010deficiency anemia. Blood coagulation analysis revealed a decreased platelet agglutination capacity, associated with reduced von Willebrand factor (vWF) antigen levels and activity. Whole\u2010genome sequencing at the age of 15\u2009years did not identify any pathogenic variants in the\n                    <jats:italic>VWF<\/jats:italic>\n                    gene. However, this analysis revealed a heterozygous pathogenic variant of\n                    <jats:italic>SOX18<\/jats:italic>\n                    (NM_018419.3: c.481C&gt;T, p.Gln161Ter), which led to the diagnosis of HLTS. SOX18 plays a significant role in\n                    <jats:italic>VWF<\/jats:italic>\n                    expression in stem cells. vWF replacement therapy facilitated safe tooth extraction and stabilized hemoglobin levels. Decreased vWF may be a complication of HLTS, and vWF replacement therapy can significantly improve patients' quality of life.\n                  <\/jats:p>","DOI":"10.1002\/ajmga.70068","type":"journal-article","created":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T11:17:21Z","timestamp":1769512641000},"page":"1384-1387","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Bleeding Diathesis in Hypotrichosis\u2013Lymphedema\u2013Telangiectasia Syndrome due to Decreased\n                    <scp>von<\/scp>\n                    Willebrand Factor"],"prefix":"10.1002","volume":"200","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4757-2121","authenticated-orcid":false,"given":"Miyako","family":"Kanno","sequence":"first","affiliation":[{"name":"Department of Pediatrics Yamagata University School of Medicine  Yamagata Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroko","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Yamagata University School of Medicine  Yamagata Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuta","family":"Uemura","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Yamagata University School of Medicine  Yamagata Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toru","family":"Meguro","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Yamagata University School of Medicine  Yamagata Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryusuke","family":"Ishigaki","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Yamagata University School of Medicine  Yamagata Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naomi","family":"Kawasaki","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Yamagata University School of Medicine  Yamagata Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masayuki","family":"Abiko","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Yamagata University School of Medicine  Yamagata Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kota","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Yamagata University School of Medicine  Yamagata Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chikahiko","family":"Numakura","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Yamagata University School of Medicine  Yamagata Japan"},{"name":"Department of Pediatrics and Clinical Genomics, Faculty of Medicine Saitama Medical University  Saitama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gen","family":"Tamiya","sequence":"additional","affiliation":[{"name":"Department of AI and Innovative Medicine Tohoku University Graduate School of Medicine  Sendai Japan"},{"name":"Tohoku Medical Megabank Organization Tohoku University  Sendai Japan"},{"name":"Statistical Genetics Team, RIKEN Center for Advanced Intelligence Project  Tokyo Japan"},{"name":"Department of Rare Disease Genomics Tohoku University Graduate School of Medicine  Sendai Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Takayama","sequence":"additional","affiliation":[{"name":"Department of AI and Innovative Medicine Tohoku University Graduate School of Medicine  Sendai Japan"},{"name":"Tohoku Medical Megabank Organization Tohoku University  Sendai Japan"},{"name":"Statistical Genetics Team, RIKEN Center for Advanced Intelligence Project  Tokyo Japan"},{"name":"Department of Rare Disease Genomics Tohoku University Graduate School of Medicine  Sendai Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeo","family":"Kure","sequence":"additional","affiliation":[{"name":"Department of Rare Disease Genomics Tohoku University Graduate School of Medicine  Sendai Japan"},{"name":"Miyagi Children's Hospital  Sendai Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoya","family":"Saijo","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Tohoku University Graduate School of Medicine  Sendai Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsuo","family":"Kikuchi","sequence":"additional","affiliation":[{"name":"Department of Rare Disease Genomics Tohoku University Graduate School of Medicine  Sendai Japan"},{"name":"Department of Pediatrics Tohoku University Graduate School of Medicine  Sendai Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuo","family":"Mitsui","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Yamagata University School of Medicine  Yamagata Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,27]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2022.104607"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddp219"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diff.2015.03.003"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1086\/375614"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkab820"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010020\u201020146\u20108"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cjca.2015.04.004"}],"container-title":["American 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