ArticleHuman molecular genetics2016
Dominant de novo DSP mutations cause erythrokeratodermia-cardiomyopathy syndrome.
Article in Human molecular genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.
- Diagnosis and management of very rare primary arrhythmia syndromes in children and adults: a Clinical Consensus Statement of the European Heart Rhythm Association of the ESC and the Association of Cardiovascular Nursing & Allied Professions of the ESC, endorsed by the Association for European Paediatric and Congenital Cardiology.Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2026Guideline
- Desmosomal-Type Acantholysis-A New Histologic Pattern Related to Mutations of Genes for Desmosomal Proteins.Dermatopathology (Basel, Switzerland) · 2026Article
- Lethal acantholytic epidermolysis bullosa- a report on the prenatal phenotype of two cases and a review of antenatal sonographic signs of congenital denuding skin diseases.BMC pregnancy and childbirth · 2025Review
- Article
- Desmoplakin mutation underlying autosomal dominant arrhythmogenic cardiomyopathy, palmoplantar keratoderma, and curly hair.JAAD case reports · 2023Article
- Towards a Better Understanding of Genotype-Phenotype Correlations and Therapeutic Targets for Cardiocutaneous Genes: The Importance of Functional Studies above Prediction.International journal of molecular sciences · 2022Review
- A novel desmoplakin mutation causes dilated cardiomyopathy with palmoplantar keratoderma as an early clinical sign.Journal of the European Academy of Dermatology and Venereology : JEADV · 2022Article
- Genetic Diagnostic Yield and Novel Causal Genes of Congenital Heart Disease.Frontiers in genetics · 2022Article
- Molecular Genetics of Keratinization Disorders - What's New About Ichthyosis.Acta dermato-venereologica · 2020Review
- The Role of Desmoglein 1 in Gap Junction Turnover Revealed through the Study of SAM Syndrome.The Journal of investigative dermatology · 2020Observational
- Analysis ofJournal of clinical medicine · 2020Article
- Mutations in PERP Cause Dominant and Recessive Keratoderma.The Journal of investigative dermatology · 2019Article
- Desmosomes: Essential contributors to an integrated intercellular junction network.F1000Research · 2019Review
- Desmoplakin maintains gap junctions by inhibiting Ras/MAPK and lysosomal degradation of connexin-43.The Journal of cell biology · 2018Article
- Epithelial barrier dysfunction in desmoglein-1 deficiency.The Journal of allergy and clinical immunology · 2018Article
- A compendium and functional characterization of mammalian genes involved in adaptation to Arctic or Antarctic environments.BMC genetics · 2017Article
- Mutations in KDSR Cause Recessive Progressive Symmetric Erythrokeratoderma.American journal of human genetics · 2017Article
- The Structure of the Plakin Domain of Plectin Reveals an Extended Rod-like Shape.The Journal of biological chemistry · 2016Article
- Recent advances in understanding ichthyosis pathogenesis.F1000Research · 2016Review
- Erythrokeratodermia-Cardiomyopathy Syndrome: Expanding the DSP Mutational Spectrum Beyond Proline Substitutions.Pediatric dermatologyArticle
Corrections and comments
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Authors and funding
15 authors at 6 institutions in 2 countries.
Funding
Abstract
Disorders of keratinization (DOK) show marked genotypic and phenotypic heterogeneity. In most cases, disease is primarily cutaneous, and further clinical evaluation is therefore rarely pursued. We have identified subjects with a novel DOK featuring erythrokeratodermia and initially-asymptomatic, progressive, potentially fatal cardiomyopathy, a finding not previously associated with erythrokeratodermia. We show that de novo missense mutations clustered tightly within a single spectrin repeat of DSP cause this novel cardio-cutaneous disorder, which we term erythrokeratodermia-cardiomyopathy (EKC) syndrome. We demonstrate that DSP mutations in our EKC syndrome subjects affect localization of desmosomal proteins and connexin 43 in the skin, and result in desmosome aggregation, widening of intercellular spaces, and lipid secretory defects. DSP encodes desmoplakin, a primary component of desmosomes, intercellular adhesion junctions most abundant in the epidermis and heart. Though mutations in DSP are known to cause other disorders, our cohort features the unique clinical finding of severe whole-body erythrokeratodermia, with distinct effects on localization of desmosomal proteins and connexin 43. These findings add a severe, previously undescribed syndrome featuring erythrokeratodermia and cardiomyopathy to the spectrum of disease caused by mutation in DSP, and identify a specific region of the protein critical to the pathobiology of EKC syndrome and to DSP function in the heart and skin.
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Registered trials
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