{"title":"A \"second hit\" impacts disease severity in a dominantly inherited genetic skin disorder.","authors":"Pierre A Coulombe","doi":"10.1084/jem.20242377","DOIUrl":null,"url":null,"abstract":"<p><p>In this issue of JEM, Bergson et al. (https://doi.org/10.1084/jem.20240827) identified variants in HMCN1 that co-segregate with and account for variations in disease severity in individuals with a diagnosis of epidermolysis bullosa simplex (EBS) resulting from pathogenic variants in KRT14. The authors show that hemicentin-1 binds keratin 14 at the protein level and that silencing HMCN1 expression disrupts the organization of K14-containing filaments in epidermal keratinocytes and their attachment to the extracellular matrix. These findings address the clinical heterogeneity observed in EBS, a rare genetic skin disorder, with general implications for all genodermatoses.</p>","PeriodicalId":15760,"journal":{"name":"Journal of Experimental Medicine","volume":"222 5","pages":""},"PeriodicalIF":12.6000,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11841682/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Experimental Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1084/jem.20242377","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/2/20 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
In this issue of JEM, Bergson et al. (https://doi.org/10.1084/jem.20240827) identified variants in HMCN1 that co-segregate with and account for variations in disease severity in individuals with a diagnosis of epidermolysis bullosa simplex (EBS) resulting from pathogenic variants in KRT14. The authors show that hemicentin-1 binds keratin 14 at the protein level and that silencing HMCN1 expression disrupts the organization of K14-containing filaments in epidermal keratinocytes and their attachment to the extracellular matrix. These findings address the clinical heterogeneity observed in EBS, a rare genetic skin disorder, with general implications for all genodermatoses.
期刊介绍：
Since its establishment in 1896, the Journal of Experimental Medicine (JEM) has steadfastly pursued the publication of enduring and exceptional studies in medical biology. In an era where numerous publishing groups are introducing specialized journals, we recognize the importance of offering a distinguished platform for studies that seamlessly integrate various disciplines within the pathogenesis field.
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