{
  "abstract": "Background Recessive dystrophic epidermolysis bullosa (RDEB) is a rare and severe blistering skin disorder caused by loss-of-function mutations in the type VII collagen gene ( COL7A1). The COL7A1 c.6527insC mutation is curiously prevalent among individuals with RDEB and is found worldwide in Europe and the Americas. Previous research has suggested the possibility of a Sephardic Jewish origin of the mutation; however, individuals with RDEB are not known to have predominant Jewish ancestry.Methods In this study, a global cohort of individuals with RDEB with the c.6527insC founder mutation from Spain, France, Argentina, Chile, Colombia and the USA were investigated by autosomal genotyping, pairwise identical-by-descent matching and a local ancestry analysis. Age estimation analysis was performed to determine when Jewish founders introduced the c.6527insC mutation into Iberian and Native American populations (~900 CE and 1492 CE, respectively).Results Sephardic ancestry was identified at the haplotype spanning the c.6527insC mutation in 85% of the individuals, despite mixed ancestry elsewhere in the genome and no known recent Sephardic ancestry. Identical-by-descent matching between this RDEB subpopulation and a known crypto-Jewish community in Belmonte, Portugal was also ascertained, providing support for crypto-Jewish ancestry in this RDEB subpopulation.Conclusion The identification of this unique RDEB subpopulation unified by the single most prevalent c.6527insC mutation holds great potential to facilitate promising new RDEB therapies using CRISPR Cas 9 gene and base editing. The identification of a single guide RNA allowing efficient and safe editing of this variant would represent a unique drug to treat a large cohort of patients with the same founder mutation.",
  "authors": [
    {
      "affiliations": [
        "Charles C. Gates Center for Regenerative Medicine, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, Colorado, USA",
        "Pediatric, Adolescent, and Adult Dermatology, Point Pleasant, New Jersey, USA"
      ],
      "name": "Emily Mira Warshauer"
    },
    {
      "affiliations": [
        "Gene by Gene, FamilyTreeDNA, Houston, Texas, USA"
      ],
      "name": "Paul A Maier"
    },
    {
      "affiliations": [
        "Gene by Gene, FamilyTreeDNA, Houston, Texas, USA"
      ],
      "name": "Goran Runfeldt"
    },
    {
      "affiliations": [
        "Centro de Genética y Genomica, Universidad del Desarrollo Facultad de Medicina Clínica Alemana, Santiago, Santiago Metropolitan Region, Chile",
        "Fundacion DEBRA Chile, Santiago, Chile",
        "Departamento de Bioingeniería, Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile"
      ],
      "name": "Ignacia Fuentes"
    },
    {
      "affiliations": [
        "Universidad Carlos III de Madrid, Departamento de Bioingeniería (UC3M), Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT), Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER-ISCIII), Instituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD), Madrid, Spain"
      ],
      "name": "Maria José Escamez"
    },
    {
      "affiliations": [
        "Center for Research in Genodermatosis and Epidermolysis Bullosa (CEDIGEA), Buenos Aires, Argentina",
        "National Scientific and Technical Research Council (CONICET), Buenos Aires, Argentina"
      ],
      "name": "Laura Valinotto"
    },
    {
      "affiliations": [
        "Center for Research in Genodermatosis and Epidermolysis Bullosa (CEDIGEA), Buenos Aires, Argentina"
      ],
      "name": "Monica Natale"
    },
    {
      "affiliations": [
        "Dermatology, Hospital de Clínicas José de San Martín, Buenos Aires, Buenos Aires, Argentina"
      ],
      "name": "Graciela Manzur"
    },
    {
      "affiliations": [
        "Universidad Carlos III de Madrid, Departamento de Bioingeniería (UC3M), Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT), Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER-ISCIII), Instituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD), Madrid, Spain"
      ],
      "name": "Nuria Illera"
    },
    {
      "affiliations": [
        "Universidad Carlos III de Madrid, Departamento de Bioingeniería (UC3M), Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT), Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER-ISCIII), Instituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD), Madrid, Spain"
      ],
      "name": "Marta Garcia"
    },
    {
      "affiliations": [
        "Universidad Carlos III de Madrid, Departamento de Bioingeniería (UC3M), Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT), Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER-ISCIII), Instituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD), Madrid, Spain"
      ],
      "name": "Marcela Del Rio"
    },
    {
      "affiliations": [
        "Universidad Carlos III de Madrid, Departamento de Bioingeniería (UC3M), Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT), Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER-ISCIII), Instituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD), Madrid, Spain"
      ],
      "name": "Angeles Mencia"
    },
    {
      "affiliations": [
        "Universidad Carlos III de Madrid, Departamento de Bioingeniería (UC3M), Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT), Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER-ISCIII), Instituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD), Madrid, Spain"
      ],
      "name": "Almudena Holguin"
    },
    {
      "affiliations": [
        "Universidad Carlos III de Madrid, Departamento de Bioingeniería (UC3M), Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT), Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER-ISCIII), Instituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD), Madrid, Spain",
        "Epithelial Biomedicine Division, Centre for Energy, Environment and Technology Research (CIEMAT), Madrid, Spain"
      ],
      "name": "Fernando Larcher"
    },
    {
      "affiliations": [
        "UCL Genetics Institute (UGI), Department of Genetics, Evolution and Environment, UCL, London, UK"
      ],
      "name": "Garrett Hellenthal"
    },
    {
      "affiliations": [
        "Avotaynu Foundation, Englewood, New Jersey, USA"
      ],
      "name": "Adam R Brown"
    },
    {
      "affiliations": [
        "Fundacion DEBRA Colombia, Bogotá, Colombia"
      ],
      "name": "Liliana Consuegra"
    },
    {
      "affiliations": [
        "Fundacion DEBRA Colombia, Bogotá, Colombia",
        "Medical Genetics, Universidad del Rosario, Bogotá, Bogota, Colombia"
      ],
      "name": "Carolina Rivera"
    },
    {
      "affiliations": [
        "University of Porto Institute of Molecular Pathology and Immunology, Porto, Porto District, Portugal"
      ],
      "name": "Inês Nogueiro"
    },
    {
      "affiliations": [
        "Dermatology, Stanford University, Stanford, California, USA"
      ],
      "name": "Jean Tang"
    },
    {
      "affiliations": [
        "Dermatology, Stanford University, Stanford, California, USA",
        "Program in Epithelial Biology and Department of Dermatology, Stanford University School of Medicine, Stanford, California, USA"
      ],
      "name": "Anthony Oro"
    },
    {
      "affiliations": [
        "Program in Epithelial Biology and Department of Dermatology, Stanford University School of Medicine, Stanford, California, USA"
      ],
      "name": "Peter Marinkovich"
    },
    {
      "affiliations": [
        "Fundacion DEBRA Chile, Santiago, Chile",
        "Departamento de Bioingeniería, Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile"
      ],
      "name": "Francis Palisson"
    },
    {
      "affiliations": [
        "Imagine Institute, Paris Cité University, Paris, France",
        "Laboratory of Genetic Skin Diseases, INSERM U1163, Paris, France"
      ],
      "name": "Matthias Titeux"
    },
    {
      "affiliations": [
        "Imagine Institute, Paris Cité University, Paris, France",
        "Laboratory of Genetic Skin Diseases, INSERM U1163, Paris, France",
        "Department of Genetics, Necker Hospital for Sick Children, AP-HP, Paris, France"
      ],
      "name": "Alain A Hovnanian"
    },
    {
      "affiliations": [
        "Dermatology, Tel Aviv Sourasky Medical Center, Tel Aviv-Yafo, Tel Aviv District, Israel",
        "Human Molecular Genetics, Tel Aviv University Sackler Faculty of Medicine, Tel Aviv-Yafo, Tel Aviv District, Israel"
      ],
      "name": "Eli Sprecher"
    },
    {
      "affiliations": [
        "Genetics & Developmental Biology, Technion Israel Institute of Technology The Ruth and Bruce Rappaport Faculty of Medicine, Haifa, Haifa District, Israel",
        "Nephrology, Technion Israel Institute of Technology, The Ruth and Bruce Rappaport, Faculty of Medicine, Haifa, Haifa District, Israel"
      ],
      "name": "Karl Skorecki"
    },
    {
      "affiliations": [
        "Charles C. Gates Center for Regenerative Medicine, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, Colorado, USA",
        "Dermatology, University of Colorado, Anschutz Medical Campus, School of Medicine, Aurora, Colorado, USA"
      ],
      "name": "David Norris"
    },
    {
      "affiliations": [
        "Dermatology, University of Colorado, Anschutz Medical Campus, School of Medicine, Aurora, Colorado, USA"
      ],
      "name": "Anna Bruckner"
    },
    {
      "affiliations": [
        "Charles C. Gates Center for Regenerative Medicine, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, Colorado, USA",
        "Dermatology, University of Colorado, Anschutz Medical Campus, School of Medicine, Aurora, Colorado, USA"
      ],
      "name": "Igor Kogut"
    },
    {
      "affiliations": [
        "Charles C. Gates Center for Regenerative Medicine, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, Colorado, USA",
        "Dermatology, University of Colorado, Anschutz Medical Campus, School of Medicine, Aurora, Colorado, USA"
      ],
      "name": "Ganna Bilousova"
    },
    {
      "affiliations": [
        "Charles C. Gates Center for Regenerative Medicine, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, Colorado, USA",
        "Dermatology, University of Colorado, Anschutz Medical Campus, School of Medicine, Aurora, Colorado, USA"
      ],
      "name": "Dennis Roop"
    }
  ],
  "title": "Sephardic origins revealed for rare skin disorder, recessive dystrophic epidermolysis bullosa, in individuals carrying the unique c.6527insC mutation",
  "uid": "7a422b1f-1e1f-5365-9808-45711f15b62e"
}