{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T03:43:36Z","timestamp":1773891816083,"version":"3.50.1"},"reference-count":28,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2024,3,4]],"date-time":"2024-03-04T00:00:00Z","timestamp":1709510400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100017638","name":"Ministry of Health of the Russian Federation","doi-asserted-by":"publisher","award":["123020800102-9"],"award-info":[{"award-number":["123020800102-9"]}],"id":[{"id":"10.13039\/501100017638","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Epidermolysis bullosa simplex (EBS) is a dermatological condition marked by skin fragility and blister formation resulting from separation within the basal layer of the epidermis, which can be attributed to various genetic etiologies. This study presents three pathogenic de novo variants in young children, with clinical manifestations appearing as early as the neonatal period. The variants contribute to the EBS phenotype through two distinct mechanisms: direct keratin abnormalities due to pathogenic variants in the Krt14 gene, and indirect effects via pathogenic mutation in the KLHL24 gene, which interfere with the natural proteasome-mediated degradation pathway of KRT14. We report one severe case of EBS with mottled pigmentation arising from the Met119Thr pathogenic variant in KRT14, another case involving a pathogenic KLHL24 Met1Val variant, and a third case featuring the hot spot mutation Arg125His in KRT14, all manifesting within the first few weeks of life. This research underscores the complexity of genetic influences in EBS and highlights the importance of early genetic screening for accurate diagnosis and management.<\/jats:p>","DOI":"10.3390\/ijms25052989","type":"journal-article","created":{"date-parts":[[2024,3,5]],"date-time":"2024-03-05T03:03:20Z","timestamp":1709607800000},"page":"2989","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["EBS in Children with De Novo Pathogenic Variants Disturbing Krt14"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2908-6499","authenticated-orcid":false,"given":"Anastasiya V.","family":"Kosykh","sequence":"first","affiliation":[{"name":"Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Pirogov Russian National Research Medical University, Ostrovityanova 1, Moscow 117997, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irina I.","family":"Ryumina","sequence":"additional","affiliation":[{"name":"National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V. I. Kulakov, ul Akademika Oparina, 4, Moscow 117997, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandra S.","family":"Botkina","sequence":"additional","affiliation":[{"name":"Department of Dermatovenereology, Russian Children\u2019s Clinical Hospital, Pirogov Russian National Research Medical University, Leninsky Prospekt, 117, k3, Moscow 119571, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1726-1939","authenticated-orcid":false,"given":"Nadezhda A.","family":"Evtushenko","sequence":"additional","affiliation":[{"name":"Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Pirogov Russian National Research Medical University, Ostrovityanova 1, Moscow 117997, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena B.","family":"Zhigmitova","sequence":"additional","affiliation":[{"name":"Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Pirogov Russian National Research Medical University, Ostrovityanova 1, Moscow 117997, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aleksandra A.","family":"Martynova","sequence":"additional","affiliation":[{"name":"Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Pirogov Russian National Research Medical University, Ostrovityanova 1, Moscow 117997, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8028-8176","authenticated-orcid":false,"given":"Nadya G.","family":"Gurskaya","sequence":"additional","affiliation":[{"name":"Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Pirogov Russian National Research Medical University, Ostrovityanova 1, Moscow 117997, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Denis V.","family":"Rebrikov","sequence":"additional","affiliation":[{"name":"Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Pirogov Russian National Research Medical University, Ostrovityanova 1, Moscow 117997, Russia"},{"name":"National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V. 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