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Novel variants impairing Sp1 transcription factor binding in the COL7A1 promoter cause mild cases of recessive dystrophic epidermolysis bullosa

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dc.contributor.authorPironon, Nathalie
dc.contributor.authorGasparyan, Artyom
dc.contributor.authorYubero, María
dc.contributor.authorDuchatelet, Sabine
dc.contributor.authorHovhannesyan, Kristina
dc.contributor.authorLeclerc-Mercier, Stephanie
dc.contributor.authorKostandyan, Natella
dc.contributor.authorPalisson, Francis
dc.contributor.authorSarkisian, Tamara
dc.contributor.authorTiteux, Matthias
dc.contributor.authorFuentes, Ignacia
dc.contributor.authorHovnanian, Alain
dc.date.accessioned2026-08-04T20:45:02Z
dc.date.available2026-08-04T20:45:02Z
dc.date.issued2025
dc.description.abstractRecessive dystrophic epidermolysis bullosa (RDEB) is a rare and most often severe genodermatosis characterized by recurrent blistering and erosions of the skin and mucous membranes after minor trauma, leading to major local and systemic complications. RDEB is caused by loss-of-function mutations in COL7A1 encoding type VII collagen (C7), the main component of anchoring fibrils which form attachment structures stabilizing the cutaneous basement membrane zone. Most of the previously reported COL7A1 mutations are located in the coding or intronic regions. We describe 6 patients with localized or intermediate RDEB for whom one recessive pathogenic variant in the coding region and a second variant in the COL7A1 promoter were identified. These substitutions, three of which are novel, are localized in two Sp1 binding sites of the promoter region. DNA pull-down assay showed a drastic reduction of Sp1 binding consistent with a dramatic decrease in COL7A1 transcript and almost undetectable C7 protein levels. Our results reveal that mutations in the COL7A1 promoter on the background of a null allele can underlie localized or intermediate RDEB. They further emphasize the functional importance of Sp1 motifs in the proximal COL7A1 promoter which should be carefully investigated for regulatory mutations in the case of RDEB with only one pathogenic variant identified in the coding or intronic regions.
dc.description.versionVersión Publicada
dc.identifier.citationPironon N, Gasparyan A, Yubero MJ, Duchatelet S, Hovhannesyan K, Leclerc-Mercier S, Kostandyan N, Palisson F, Sarkisian T, Titeux M, Fuentes I, Hovnanian A. Novel variants impairing Sp1 transcription factor binding in the COL7A1 promoter cause mild cases of recessive dystrophic epidermolysis bullosa. Eur J Hum Genet. 2025 Mar;33(3):344-350. doi: 10.1038/s41431-024-01717-5
dc.identifier.doihttps://doi.org/10.1038/s41431-024-01717-5
dc.identifier.urihttps://hdl.handle.net/11447/10954
dc.language.isoen
dc.subjectEpidermolysis Bullosa Dystrophica* / metabolism
dc.subjectEpidermolysis Bullosa Dystrophica* / pathology
dc.subjectSp1 Transcription Factor* / genetics
dc.subjectSp1 Transcription Factor* / metabolism
dc.titleNovel variants impairing Sp1 transcription factor binding in the COL7A1 promoter cause mild cases of recessive dystrophic epidermolysis bullosa
dc.typeArticle
dcterms.accessRightsAcceso Abierto
dcterms.sourceEuropean journal of human genetics : EJHG
dspace.entity.typePublication

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