{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,26]],"date-time":"2026-07-26T15:02:15Z","timestamp":1785078135330,"version":"3.55.0"},"reference-count":22,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T00:00:00Z","timestamp":1784937600000},"content-version":"vor","delay-in-days":24,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"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":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Multifocal sporadic venous malformations (MSVM) are a rare and severe subtype of venous malformations (VMs). Although somatic mutations in the\n                      <jats:italic>TEK<\/jats:italic>\n                      gene are frequently implicated in VMs, the clinical and molecular significance of harboring two distinct somatic mutations within a single lesion remains poorly understood.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>DNA was extracted from both the lesion and peripheral blood, followed by whole\u2010exome sequencing (WES) and structural modeling of the TIE2 protein.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The proband, a 6\u2010year\u2010old Chinese boy, presented at birth with soft\u2010tissue swelling of the hands and occipital region, which progressively involved the tongue, neck, trunk, extremities, and external genitalia. Imaging demonstrated extensive venous ectasia infiltrating subcutaneous and muscular layers. Despite 20 sessions of sclerotherapy, the lesions continued to progress and showed a strong tendency for recurrence. WES of the lesion revealed two pathogenic somatic mutations in the\n                      <jats:italic>TEK<\/jats:italic>\n                      gene: c.2740C&gt;T (p.L914F) and c.2545C&gt;T (p.R849W), which weren't detected in peripheral blood. Structural modeling suggested no major global conformational changes but showed possible local structural differences within the kinase domain. The double\u2010mutant variant exhibited predicted enhanced hydrogen bonding at the mutation sites, potentially contributing to local structural rearrangements and altered conformational stability.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      This report describes a previously unreported case of dual somatic\n                      <jats:italic>TEK<\/jats:italic>\n                      mutations in MSVM. The findings expand the mutational spectrum of\n                      <jats:italic>TEK<\/jats:italic>\n                      \u2010related VMs and underscore the importance of lesion\u2010based genetic testing in complex cases.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mgg3.70269","type":"journal-article","created":{"date-parts":[[2026,7,26]],"date-time":"2026-07-26T06:15:56Z","timestamp":1785046556000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Multifocal Sporadic Venous Malformations in a Child Caused by a Novel Somatic Double Mutation of the\n                    <i>TEK<\/i>\n                    Gene: A Case Report and Literature Review"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0944-2692","authenticated-orcid":false,"given":"Lu","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Pediatric Cardiology, West China Second University Hospital Sichuan University  Chengdu Sichuan China"},{"name":"Key Laboratory of Birth Defect and Related Diseases of Women and Children (Sichuan University) Ministry of Education  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9345-389X","authenticated-orcid":false,"given":"Yidan","family":"Cao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Birth Defect and Related Diseases of Women and Children (Sichuan University) Ministry of Education  Chengdu Sichuan China"},{"name":"Department of Pathology, West China Second University Hospital Sichuan University  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunhua","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Pediatric Cardiology, West China Second University Hospital Sichuan University  Chengdu Sichuan China"},{"name":"Key Laboratory of Birth Defect and Related Diseases of Women and Children (Sichuan University) Ministry of Education  Chengdu Sichuan China"},{"name":"The Affiliated Hospital of Southwest Jiaotong University, the Third People's Hospital of Chengdu  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2583-4058","authenticated-orcid":false,"given":"Fan","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Pediatric Cardiology, West China Second University Hospital Sichuan University  Chengdu Sichuan China"},{"name":"Key Laboratory of Birth Defect and Related Diseases of Women and Children (Sichuan University) Ministry of Education  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,25]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI76004"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1177\/0268355520972918"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aaf1164"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.sempedsurg.2020.150976"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10456\u2010018\u20109624\u20107"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humimm.2021.02.012"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jvs.2021.04.071"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41433\u2010020\u201001377\u2010x"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcpt.13027"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.118.312315"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2015.11.011"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.272"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.23736\/S0021\u20109509.21.11911\u20101"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddv349"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s10038\u2010022\u201001081\u20106"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddaf169"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lpm.2025.104295"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom14050568"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2016.07.034"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1159\/000348327"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092\u20108674(00)81814\u20100"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2009.193"}],"container-title":["Molecular Genetics &amp; 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