{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T22:12:31Z","timestamp":1784585551762,"version":"3.55.0"},"reference-count":47,"publisher":"Georg Thieme Verlag KG","issue":"07","funder":[{"name":"Spanish Ministry of the Economy and Competitiveness"},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"crossref","award":["PI18\/01492"],"award-info":[{"award-number":["PI18\/01492"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Real Fundaci\u00f3n Victoria Eugenia"},{"name":"Fundaci\u00f3 Privada Catalana de l'Hemof\u00edlia"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Thromb Haemost"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:p>\n            Introduction\u2003Investigation of the molecular basis of inherited bleeding disorders (IBD) is mostly performed with gene panel sequencing. However, the continuous discovery of new related genes underlies the limitation of this approach. This study aimed to identify genetic variants responsible for IBD in pediatric patients using whole-exome sequencing (WES), and to provide a detailed description and reclassification of candidate variants.<\/jats:p><jats:p>\n            Material and Methods\u2003WES was performed for 18 pediatric patients, and variants were filtered using a first-line list of 290 genes. Variant prioritization was discussed in a multidisciplinary team based on genotype-phenotype correlation, and segregation studies were performed with available family members.<\/jats:p><jats:p>\n            Results\u2003The study identified 22 candidate variants in 17 out of 18 patients (94%). Eleven patients had complete genotype-phenotype correlation, resulting in a diagnostic yield of 61%, 5 (28%) were classified as partially solved, and 2 (11%) remained unsolved. Variants were identified in platelet (ACTN1, ANKRD26, CYCS, GATA1, GFI1B, ITGA2, NBEAL2, RUNX1, SRC, TUBB1), bleeding (APOLD1), and coagulation (F7, F8, F11, VWF) genes. Notably, 9 out of 22 (41%) variants were previously unreported. Variant pathogenicity was assessed according to the American College of Medical Genetics and Genomics guidelines and reclassification of three variants based on family segregation evidence, resulting in the identification of 10 pathogenic or likely pathogenic variants, 6 variants of uncertain significance, and 6 benign or likely benign variants.<\/jats:p><jats:p>\n            Conclusion\u2003This study demonstrated the high potential of WES in identifying rare molecular defects causing IBD in pediatric patients, improving their management, prognosis, and treatment, particularly for patients at risk of malignancy and\/or bleeding due to invasive procedures.<\/jats:p>","DOI":"10.1055\/s-0043-1778070","type":"journal-article","created":{"date-parts":[[2023,12,30]],"date-time":"2023-12-30T00:22:47Z","timestamp":1703895767000},"page":"628-640","source":"Crossref","is-referenced-by-count":4,"title":["Gaining Insights into Inherited Bleeding Disorders of Complex Etiology in Pediatric Patients: Whole-Exome Sequencing as First-Line Investigation Tool"],"prefix":"10.1055","volume":"124","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6002-7454","authenticated-orcid":false,"given":"Perla","family":"Bandini","sequence":"additional","affiliation":[{"name":"Laboratori de Coagulopaties Cong\u00e8nites, Banc de Sang i Teixits, Barcelona, Spain"},{"name":"Medicina Transfusional, Vall d'Hebron Institut de Recerca, Universitat Aut\u00f2noma de Barcelona (VHIR-UAB), Barcelona, Spain"},{"name":"Departament de Gen\u00e8tica, Microbiologia i Estad\u00edstica, Universitat de Barcelona, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"Borr\u00e0s","sequence":"additional","affiliation":[{"name":"Laboratori de Coagulopaties Cong\u00e8nites, Banc de Sang i Teixits, Barcelona, Spain"},{"name":"Medicina Transfusional, Vall d'Hebron Institut de Recerca, Universitat Aut\u00f2noma de Barcelona (VHIR-UAB), Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruben","family":"Berrueco","sequence":"additional","affiliation":[{"name":"Servei d'Hematologia Pedi\u00e0trica, Hospital Sant Joan de D\u00e9u Barcelona, Institut de Recerca Pedi\u00e0trica, Hospital Sant Joan de D\u00e9u de Barcelona (IRP-HSJD), Universitat de Barcelona, Barcelona, Spain"},{"name":"Instituto Nacional de Investigaci\u00f3n Biom\u00e9dica en Enfermedades Raras (CIBER ER), Instituto de Salud Carlos III, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanna","family":"Gassiot","sequence":"additional","affiliation":[{"name":"Servei de Diagn\u00f2stic de Laboratori, Hospital Sant Joan de D\u00e9u Barcelona, Institut de Recerca Pedi\u00e0trica, Hospital Sant Joan de D\u00e9u de Barcelona (IRP-HSJD), Universitat de Barcelona, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8909-508X","authenticated-orcid":false,"given":"Laura","family":"Martin-Fernandez","sequence":"additional","affiliation":[{"name":"Laboratori de Coagulopaties Cong\u00e8nites, Banc de Sang i Teixits, Barcelona, Spain"},{"name":"Medicina Transfusional, Vall d'Hebron Institut de Recerca, Universitat Aut\u00f2noma de Barcelona (VHIR-UAB), Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edurne","family":"Sarrate","sequence":"additional","affiliation":[{"name":"Servei de Diagn\u00f2stic de Laboratori, Hospital Sant Joan de D\u00e9u Barcelona, Institut de Recerca Pedi\u00e0trica, Hospital Sant Joan de D\u00e9u de Barcelona (IRP-HSJD), Universitat de Barcelona, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nat\u00e0lia","family":"Comes","sequence":"additional","affiliation":[{"name":"Laboratori de Coagulopaties Cong\u00e8nites, Banc de Sang i Teixits, Barcelona, Spain"},{"name":"Medicina Transfusional, Vall d'Hebron Institut de Recerca, Universitat Aut\u00f2noma de Barcelona (VHIR-UAB), Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorena","family":"Ram\u00edrez","sequence":"additional","affiliation":[{"name":"Laboratori de Coagulopaties Cong\u00e8nites, Banc de Sang i Teixits, Barcelona, Spain"},{"name":"Medicina Transfusional, Vall d'Hebron Institut de Recerca, Universitat Aut\u00f2noma de Barcelona (VHIR-UAB), Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Hobeich","sequence":"additional","affiliation":[{"name":"Laboratori de Coagulopaties Cong\u00e8nites, Banc de Sang i Teixits, Barcelona, Spain"},{"name":"Medicina Transfusional, Vall d'Hebron Institut de Recerca, Universitat Aut\u00f2noma de Barcelona (VHIR-UAB), Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8089-4945","authenticated-orcid":false,"given":"Francisco","family":"Vidal","sequence":"additional","affiliation":[{"name":"Laboratori de Coagulopaties Cong\u00e8nites, Banc de Sang i Teixits, Barcelona, Spain"},{"name":"Medicina Transfusional, Vall d'Hebron Institut de Recerca, Universitat Aut\u00f2noma de Barcelona (VHIR-UAB), Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Cardiovasculares (CIBERCV). Instituto de Salud Carlos III (ISCIII), Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Corrales","sequence":"additional","affiliation":[{"name":"Laboratori de Coagulopaties Cong\u00e8nites, Banc de Sang i Teixits, Barcelona, Spain"},{"name":"Medicina Transfusional, Vall d'Hebron Institut de Recerca, Universitat Aut\u00f2noma de Barcelona (VHIR-UAB), Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Cardiovasculares (CIBERCV). 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