{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T22:31:06Z","timestamp":1793313066136,"version":"4.5.0"},"reference-count":28,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,3,11]],"date-time":"2024-03-11T00:00:00Z","timestamp":1710115200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acad Dermatol Venereol"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Genome diagnostics is considered gold standard diagnostics for epidermolysis bullosa (EB), a phenotypically and genetically heterogeneous group of rare disorders characterized by blistering and wounding of mucocutaneous tissues. EB is caused by pathogenic variants in genes encoding proteins of the dermo\u2010epidermal junction. Accurate genetic diagnosis of EB is crucial for prognostication, counselling and precision\u2010medicine. Genome diagnostics for EB started in 1991 with the introduction of Sanger sequencing (SS), analysing one gene at a time. In 2013, SS was superseded by next\u2010generation sequencing (NGS), that allow for high\u2010throughput sequencing of multiple genes in parallel. Several studies have shown a beneficial role for NGS in EB diagnostics, but its true benefit has not been quantified.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>To determine the benefit of NGS in EB by systematically evaluating the performance of different genome diagnostics used over time based on robust data from the Dutch EB Registry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The diagnostic performances of SS and NGS were systematically evaluated in a retrospective observational study including all index cases with a clinical diagnosis of EB in whom genome diagnostics was performed between 01 January 1994 and 01 January 2022 (<jats:italic>n<\/jats:italic>\u2009=\u2009308), registered at the Dutch EB Expertise Centre.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Over time, a genetic diagnosis was made in 289\/308 (94%) EB cases. The diagnostic yield increased from 89% (SS) to 95% (NGS). Most importantly, NGS significantly reduced diagnostic turnaround time (39\u2009days vs. 211\u2009days, <jats:italic>p\u2009&lt;<\/jats:italic>\u20090.001). The likelihood of detecting variants of uncertain significance and additional findings increased from 5% and 1% (SS) to 22% and 13% (NGS) respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our study quantifies the benefit of NGS\u2010based methods and demonstrate they have had a major impact on EB diagnostics through an increased diagnostic yield and a dramatically decreased turnaround time (39\u2009days). Although our diagnostic yield is high (95%), further improvement of genome diagnostics is urgently needed to provide a genetic diagnosis in all EB patients.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jdv.19938","type":"journal-article","created":{"date-parts":[[2024,3,11]],"date-time":"2024-03-11T09:20:01Z","timestamp":1710148801000},"page":"154-160","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Evolution of genome diagnostics in epidermolysis bullosa: Unveiling the power of next\u2010generation sequencing"],"prefix":"10.1111","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6440-4915","authenticated-orcid":false,"given":"R.","family":"Baardman","sequence":"first","affiliation":[{"name":"Department of Dermatology, UMCG Centers of Expertise for Blistering Diseases and Genodermatoses University of Groningen, University Medical Center Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. H.","family":"Lemmink","sequence":"additional","affiliation":[{"name":"Department of Genetics, UMCG Centers of Expertise for Blistering Diseases and Genodermatoses University of Groningen, University Medical Center Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0502-9665","authenticated-orcid":false,"given":"V. K.","family":"Yenamandra","sequence":"additional","affiliation":[{"name":"Academy of Scientific and Innovative Research South Campus CSIR\u2010Institute of Genomics and Integrative Biology (IGIB)  New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. Z.","family":"Commandeur\u2010Jan","sequence":"additional","affiliation":[{"name":"Department of Genetics, UMCG Centers of Expertise for Blistering Diseases and Genodermatoses University of Groningen, University Medical Center Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Viel","sequence":"additional","affiliation":[{"name":"Department of Genetics, UMCG Centers of Expertise for Blistering Diseases and Genodermatoses University of Groningen, University Medical Center Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. A.","family":"Kooi","sequence":"additional","affiliation":[{"name":"Department of Genetics, UMCG Centers of Expertise for Blistering Diseases and Genodermatoses University of Groningen, University Medical Center Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8053-216X","authenticated-orcid":false,"given":"G. F. H.","family":"Diercks","sequence":"additional","affiliation":[{"name":"Department of Dermatology, UMCG Centers of Expertise for Blistering Diseases and Genodermatoses University of Groningen, University Medical Center Groningen  Groningen The Netherlands"},{"name":"Department of Pathology, UMCG Centers of Expertise for Blistering Diseases and Genodermatoses University of Groningen, University Medical Center Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Meijer","sequence":"additional","affiliation":[{"name":"Department of Genetics, University Medical Center Nijmegen University of Nijmegen  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0273-8020","authenticated-orcid":false,"given":"M.","family":"van Geel","sequence":"additional","affiliation":[{"name":"Department of Genetics, Maastricht University Medical Center University of Maastricht  Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2986-0915","authenticated-orcid":false,"given":"H.","family":"Scheffer","sequence":"additional","affiliation":[{"name":"Department of Genetics, University Medical Center Nijmegen University of Nijmegen  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0497-4780","authenticated-orcid":false,"given":"R. J.","family":"Sinke","sequence":"additional","affiliation":[{"name":"Department of Genetics, UMCG Centers of Expertise for Blistering Diseases and Genodermatoses University of Groningen, University Medical Center Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2239-9054","authenticated-orcid":false,"given":"B.","family":"Sikkema\u2010Raddatz","sequence":"additional","affiliation":[{"name":"Department of Genetics, UMCG Centers of Expertise for Blistering Diseases and Genodermatoses University of Groningen, University Medical Center Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2086-9363","authenticated-orcid":false,"given":"M. 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