biostudies-literatureCohen-Barak ENational Institute of Arthritis and Musculoskeletal and Skin DiseasesSense About ScienceNorthwestern UniversityNCI NIH HHSNational Institutes of HealthNIAMS NIH HHSFulbright Association556-567.e9https://www.ebi.ac.uk/biostudies/studies/S-EPMC7039747biostudies-literatureUnknown140(3)An effective epidermal barrier requires structural and functional integration of adherens junctions, tight junctions, gap junctions (GJ), and desmosomes. Desmosomes govern epidermal integrity while GJs facilitate small molecule transfer across cell membranes. Some patients with severe dermatitis, multiple allergies, and metabolic wasting (SAM) syndrome, caused by biallelic desmoglein 1 (DSG1) mutations, exhibit skin lesions reminiscent of erythrokeratodermia variabilis, caused by mutations in connexin (Cx) genes. We, therefore, examined whether SAM syndrome-causing DSG1 mutations interfere with Cx expression and GJ function. Lesional skin biopsies from SAM syndrome patients (n = 7) revealed decreased Dsg1 and Cx43 plasma membrane localization compared with control and nonlesional skin. CulThe Journal of investigative dermatologyThe Role of Desmoglein 1 in Gap Junction Turnover Revealed through the Study of SAM Syndrome.PMC70397475P30AR057216R01 AR041836R37 AR43380R37 AR043380R01 CA228196P30 AR057216T32 CA009560Johnson JLRozenblat MKrausz JHarmon RKhayat MGodsel LMGreen KJShalev SAKushnir-Grinbaum DKoetsier JLDanial-Farran NZiv MSarig OSprecher EHammad HPeled AHegazy MBochner RCohen-Barak EfalseThe Role of Desmoglein 1 in Gap Junction Turnover Revealed through the Study of SAM Syndrome.An effective epidermal barrier requires structural and functional integration of adherens junctions, tight junctions, gap junctions (GJ), and desmosomes. Desmosomes govern epidermal integrity while GJs facilitate small molecule transfer across cell membranes. Some patients with severe dermatitis, multiple allergies, and metabolic wasting (SAM) syndrome, caused by biallelic desmoglein 1 (DSG1) mutations, exhibit skin lesions reminiscent of erythrokeratodermia variabilis, caused by mutations in connexin (Cx) genes. We, therefore, examined whether SAM syndrome-causing DSG1 mutations interfere with Cx expression and GJ function. Lesional skin biopsies from SAM syndrome patients (n = 7) revealed decreased Dsg1 and Cx43 plasma membrane localization compared with control and nonlesional skin. Cul2020-01-01T00:00:00Z2020 Mar2025-04-19T02:20:46.859Z2021-03-03T08:08:28ZS-EPMC70397473146573810.1016/j.jid.2019.08.433