Work

A “second hit” impacts disease severity in a dominantly inherited genetic skin disorder

Year: 2025

Type: article

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.

Source: The Journal of Experimental Medicine

DOI: 10.1084/jem.20242377

Author: Pierre A. Coulombe

Institutions: University of Michigan, Michigan Medicine, U-M Rogel Cancer Center

Language: English

Topic: Skin and Cellular Biology Research

Subfield: Cell Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: bronze

Funders: National Institutes of Health, National Institute of Arthritis and Musculoskeletal and Skin Diseases