{
  "abstract": "Background Potocki-Lupski syndrome (PTLS) is a rare genetic disorder, with an estimated prevalence of 1:25 000. Detection of a duplication at position 17p11.2 comprising the RAI1 gene establishes the diagnosis. Deletion of this same region is responsible for Smith-Magenis syndrome (SMS). Hitherto, the non-specific clinical features included psychomotor and growth retardation and multiple congenital anomalies. Our aim was to further delineate the clinical spectrum of PLTS.Methods We gathered a series of 56 individuals carrying a 17p11.2 duplication, one of the largest reported to date. We collected detailed phenotypic data and established a phenotypic comparison with individuals already described in the literature.Results We corroborated the main clinical signs associated with PTLS and highlighted additional features present in a significant proportion in our series, such as intrauterine growth retardation or low birth weight, musculoskeletal and ophthalmological anomalies, and abnormalities of the skin appendages. In line with previous reports, behavioural disorders were frequently identified (23%). Yet unexpectedly, self-aggressive and hetero-aggressive behaviours, characteristic features of SMS, were found in a small number of individuals. Forty-six individuals harboured the recurrent duplication (85%), five had larger duplications (9%) and three had smaller duplications (6%). We did not identify inherited duplications when parental information was available (n=43).Conclusion Our study refined the clinical features of PTLS and their relative frequencies. Our findings therefore contribute to improving management of people with PTLS. These open up new pathophysiological hypotheses involving RAI1 gene dosage of the genesis and control of behaviour, as well as new, more complex regulatory pathways.",
  "authors": [
    {
      "affiliations": [
        "Univ. Grenoble Alpes, Inserm U1209, IAB, CHU Grenoble Alpes, Grenoble, France"
      ],
      "name": "Alicia Coudert"
    },
    {
      "affiliations": [
        "Univ. Grenoble Alpes, Inserm U1209, IAB, CHU Grenoble Alpes, Grenoble, France"
      ],
      "name": "Pauline Le Tanno"
    },
    {
      "affiliations": [
        "Univ. Grenoble Alpes, Inserm U1209, IAB, CHU Grenoble Alpes, Grenoble, France"
      ],
      "name": "William Dufour"
    },
    {
      "affiliations": [
        "Hospices Civils de Lyon, Lyon, France"
      ],
      "name": "Patrick Edery"
    },
    {
      "affiliations": [
        "Service de génétique, CHICAM Site Alençon, Alençon, France"
      ],
      "name": "Aurelia Jacquette"
    },
    {
      "affiliations": [
        "Unité de génétique constitutionnelle, service de biologie médicale, CH Versailles, Le Chesnay, France"
      ],
      "name": "Geoffroy Delplancq"
    },
    {
      "affiliations": [
        "Laboratoire de Cytogénétique, CHU Rouen, Rouen, France"
      ],
      "name": "Pascale Chambon"
    },
    {
      "affiliations": [
        "Département de Génétique médicale, Hôpital de la Timone-Enfant, Assistance Publique Hôpitaux de Marseille, Hopital de la Timone, Marseille, France"
      ],
      "name": "Chantal Missirian"
    },
    {
      "affiliations": [
        "Service de génétique clinique, CHU Lille, Lille, France"
      ],
      "name": "Roseline Caumes"
    },
    {
      "affiliations": [
        "Centre de Génétique et Centre de Référence Anomalies du Développement et Syndromes Malformatifs, FHU TRANSLAD, CHU Dijon, Dijon, France"
      ],
      "name": "Laurence Faivre"
    },
    {
      "affiliations": [
        "Laboratoire de génétique chromosomique et moléculaire, CHU Dijon, Dijon, France"
      ],
      "name": "Patrick Callier"
    },
    {
      "affiliations": [
        "Laboratoire de génétique chromosomique et moléculaire, CHU Dijon, Dijon, France"
      ],
      "name": "Anne-laure Mosca"
    },
    {
      "affiliations": [
        "Laboratoire de génétique chromosomique et moléculaire, CHU Dijon, Dijon, France"
      ],
      "name": "Nathalie Marle"
    },
    {
      "affiliations": [
        "Université Montpellier, U1183, Service de Génétique Médicale, CHU Montpellier, Montpellier, France"
      ],
      "name": "David Geneviève"
    },
    {
      "affiliations": [
        "Service de Génétique Médicale et Centre de Référence Anomalies du Développement et Syndromes Malformatifs, CHU Bordeaux",
        "INSERM U1211, Bordeaux, France"
      ],
      "name": "Didier Lacombe"
    },
    {
      "affiliations": [
        "Service de Cytogénétique - Secteur constitutionnel, CHU Clermont-Ferrand, Clermont-Ferrand, France"
      ],
      "name": "Céline Pebrel-Richard"
    },
    {
      "affiliations": [
        "Service de Génétique Médicale et Biologie de la Reproduction, CHU de Brest, Brest, France and Univ Brest, Inserm, EFS, UMR 1078, GGB, F-29200, Brest, France"
      ],
      "name": "Sylvia Redon"
    },
    {
      "affiliations": [
        "Service de génétique clinique chromosomique et moléculaire, CHU Saint-Etienne, Saint Etienne, France"
      ],
      "name": "Renaud Touraine"
    },
    {
      "affiliations": [
        "Service de génétique clinique, centre de référence maladies rares anomalies du développement CLAD-Ouest, CHU, Rennes, France"
      ],
      "name": "Melanie Fradin"
    },
    {
      "affiliations": [
        "Service de génétique clinique, centre de référence maladies rares anomalies du développement CLAD-Ouest, CHU, Rennes, France"
      ],
      "name": "Sylvie Odent"
    },
    {
      "affiliations": [
        "Service de génétique clinique, centre de référence maladies rares anomalies du développement CLAD-Ouest, CHU, Rennes, France"
      ],
      "name": "Laurent Pasquier"
    },
    {
      "affiliations": [
        "Department of Genetics, University Hospital of Angers, Angers, France"
      ],
      "name": "Agnès Guichet"
    },
    {
      "affiliations": [
        "Université de Rennes 1, UEB, IFR 140, Faculté de Médecine, CNRS, UMR 6061, Institut Génétique et Développement de Rennes, Rennes, France",
        "Medical Genetics, Centre Hospitalier Universitaire de Nantes, Nantes, France"
      ],
      "name": "Sandra Mercier"
    },
    {
      "affiliations": [
        "Medical Genetics, Centre Hospitalier Universitaire de Nantes, Nantes, France"
      ],
      "name": "Mathilde Nizon"
    },
    {
      "affiliations": [
        "Medical Genetics, Centre Hospitalier Universitaire de Nantes, Nantes, France"
      ],
      "name": "Bertrand Isidor"
    },
    {
      "affiliations": [
        "Medical Genetics, Centre Hospitalier Universitaire de Nantes, Nantes, France"
      ],
      "name": "Marie Vincent"
    },
    {
      "affiliations": [
        "LabCom I3M-Dactim mis/LMA CNRS 7348, Université de Poitiers, Poitiers, France"
      ],
      "name": "Xavier Maximin Le Guillou Horn"
    },
    {
      "affiliations": [
        "Univ. Grenoble Alpes, Inserm U1209, IAB, CHU Grenoble Alpes, Grenoble, France"
      ],
      "name": "Matthieu Egloff"
    },
    {
      "affiliations": [
        "Hôpitaux Universitaires de Strasbourg, Service de Génétique Médicale, Strasbourg, France"
      ],
      "name": "Elise Schaefer"
    },
    {
      "affiliations": [
        "Univ. Grenoble Alpes, Inserm U1209, IAB, CHU Grenoble Alpes, Grenoble, France"
      ],
      "name": "Anne-Marie Guerrot"
    },
    {
      "affiliations": [
        "Univ. Grenoble Alpes, Inserm U1209, IAB, CHU Grenoble Alpes, Grenoble, France"
      ],
      "name": "Lyse Ruaud"
    },
    {
      "affiliations": [
        "Univ. Grenoble Alpes, Inserm U1209, IAB, CHU Grenoble Alpes, Grenoble, France"
      ],
      "name": "Nicole Chemaly"
    },
    {
      "affiliations": [
        "Univ. Grenoble Alpes, Inserm U1209, IAB, CHU Grenoble Alpes, Grenoble, France"
      ],
      "name": "Gwenaël Nadeau"
    },
    {
      "affiliations": [
        "Univ. Grenoble Alpes, Inserm U1209, IAB, CHU Grenoble Alpes, Grenoble, France"
      ],
      "name": "Charles Coutton"
    },
    {
      "affiliations": [
        "Univ. Grenoble Alpes, Inserm U1209, IAB, CHU Grenoble Alpes, Grenoble, France"
      ],
      "name": "Klaus Dieterich"
    }
  ],
  "title": "Phenotypic description of a large French series of individuals with Potocki-Lupski syndrome",
  "uid": "ca5e67c3-7af1-5644-81a1-be01e0849c22"
}