{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T21:40:41Z","timestamp":1773265241601,"version":"3.50.1"},"reference-count":33,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T00:00:00Z","timestamp":1773187200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI23\/00161, CD24\/00011"],"award-info":[{"award-number":["PI23\/00161, CD24\/00011"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Hereditary angioedema due to\n                    <jats:italic>F12<\/jats:italic>\n                    pathogenic variants (HAE-FXII) is a rare autosomal dominant disorder characterized by recurrent episodes of angioedema mediated by bradykinin, incomplete penetrance, and marked sex-dependent clinical expression. Most affected individuals carry the recurrent\n                    <jats:italic>F12<\/jats:italic>\n                    c.983C&amp;gt;A\/p.Thr328Lys (T328K) founder variant. Here, we report the first documented transmission of HAE-FXII through sperm donation. The index case was an 18-year-old woman with recurrent estrogen-dependent angioedema, normal C1-inhibitor levels and function, and poor response to conventional antiallergic therapy. Molecular analysis identified the heterozygous\n                    <jats:italic>F12<\/jats:italic>\n                    T328K variant. Familial investigation revealed the same variant in her asymptomatic twin brother, while their mother tested negative, strongly suggesting paternal transmission. The fertility clinic was contacted, and genetic testing confirmed that the sperm donor was a heterozygous carrier of the\n                    <jats:italic>F12<\/jats:italic>\n                    T328K variant. Women who had conceived using this donor\u2019s sperm were subsequently notified. Through this process, a second unrelated family was identified, in which a young woman was also found to carry the heterozygous\n                    <jats:italic>F12<\/jats:italic>\n                    T328K variant and is currently asymptomatic under specialist follow-up. This study provides the first direct evidence of transmission of HAE-FXII through assisted reproductive technologies. Our findings highlight how autosomal dominant disorders with incomplete and sex-dependent penetrance can remain clinically silent in donors and be unknowingly transmitted to multiple offspring. These observations have important implications for genetic counseling, donor notification strategies, and donor screening policies, and support consideration of targeted screening for recurrent pathogenic variants such as\n                    <jats:italic>F12<\/jats:italic>\n                    T328K in regions where HAE-FXII is more prevalent.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1799395","type":"journal-article","created":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T05:36:08Z","timestamp":1773207368000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Transmission of F12-related hereditary angioedema through a sperm donor"],"prefix":"10.3389","volume":"17","author":[{"given":"Llu\u00eds","family":"Marqu\u00e8s","sequence":"first","affiliation":[{"name":"Allergy Department, Hospital Universitari Arnau de Vilanova, Institut de Recerca Biom\u00e8dica de Lleida (IRBLlleida)","place":["Lleida, Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Batlle-Mas\u00f3","sequence":"additional","affiliation":[{"name":"Translational Immunology Group, Vall d\u2019Hebron Research Institute (VHIR)","place":["Barcelona, Spain"]},{"name":"Immunology Division, Hospital Universitari Vall d\u2019Hebron (HUVH)","place":["Barcelona, Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eva","family":"Alcoceba","sequence":"additional","affiliation":[{"name":"Allergy Department, Hospital Universitari de Santa Maria, Institut de Recerca Biom\u00e8dica de Lleida (IRBLlleida)","place":["Lleida, Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvia","family":"Lara","sequence":"additional","affiliation":[{"name":"Allergy Department, Hospital Universitari de Santa Maria, Institut de Recerca Biom\u00e8dica de Lleida (IRBLlleida)","place":["Lleida, Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aina","family":"Aguil\u00f3-Cucurull","sequence":"additional","affiliation":[{"name":"Translational Immunology Group, Vall d\u2019Hebron Research Institute (VHIR)","place":["Barcelona, Spain"]},{"name":"Immunology Division, Hospital Universitari Vall d\u2019Hebron (HUVH)","place":["Barcelona, Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johana","family":"Gil-Serrano","sequence":"additional","affiliation":[{"name":"Department of Allergy, Hospital Universitari Vall d\u2019Hebron (HUVH)","place":["Barcelona, Spain"]},{"name":"Allergy Research Unit, Vall d\u2019Hebron Research Institute (VHIR)","place":["Barcelona, Spain"]},{"name":"Department of Medicine, Autonomous University of Barcelona (UAB)","place":["Bellaterra, Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar","family":"Guilarte","sequence":"additional","affiliation":[{"name":"Department of Allergy, Hospital Universitari Vall d\u2019Hebron (HUVH)","place":["Barcelona, Spain"]},{"name":"Allergy Research Unit, Vall d\u2019Hebron Research Institute (VHIR)","place":["Barcelona, Spain"]},{"name":"Department of Medicine, Autonomous University of Barcelona (UAB)","place":["Bellaterra, Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roger","family":"Colobran","sequence":"additional","affiliation":[{"name":"Translational Immunology Group, Vall d\u2019Hebron Research Institute (VHIR)","place":["Barcelona, Spain"]},{"name":"Immunology Division, Hospital Universitari Vall d\u2019Hebron (HUVH)","place":["Barcelona, Spain"]},{"name":"Department of Clinical and Molecular Genetics, Hospital Universitari Vall d\u2019Hebron (HUVH)","place":["Barcelona, Spain"]},{"name":"Department of Cell Biology, Physiology and Immunology, Autonomous University of Barcelona (UAB)","place":["Bellaterra, 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