{
  "abstract": "Background Pathogenic gain-of-function or dominant-negative effect missense variations in ACTB are associated with a neurodevelopmental disorder characterised by intellectual disability (ID), seizures, sensorineural hearing loss, cerebral, renal and ocular abnormalities and dysmorphic features (Baraitser-Winter cerebrofrontofacial syndrome). ACTB encodes beta-actin, a highly conserved protein involved in cell motility, structure and integrity. Deletions including ACTB, and, more rarely, single-nucleotide loss-of-function variants in ACTB have been described in patients with a distinct phenotype including developmental delay, ID, microcephaly, growth restriction, cardiac and renal abnormalities and dysmorphic features.Methods We collected 14 individuals and 1 fetus carrying a heterozygous deletion including ACTB, and 4 individuals with a heterozygous truncating variant. Genotypic and phenotypic data were analysed. Furthermore, a comprehensive review of all cases reported to date was also undertaken.Results Twelve out of 17 individuals presented with ID, and 3 out of 17 with learning disabilities. Speech delay and behavioural abnormalities were observed in 15 out of 17 and 12 out of 17 individuals, respectively, motor delay in 9 out of 17 and growth restriction in 9 out of 18. Most of the individuals (13/18) had recognisable dysmorphic features. 11 anomalies were de novo, except for 1 deletion inherited from the mother. The size of the deletion varied from 125 kb to 1.6 Mb and could result from a fork stalling and template switching.Conclusion This study allowed us to better characterise the phenotype associated with the haploinsufficiency of ACTB, underlying the high prevalence of neurodevelopmental disorders (ID, speech and motor delay, behavioural abnormalities) and growth restriction in this recognisable syndrome.",
  "authors": [
    {
      "affiliations": [
        "Fédération de Génétique et Médecine Génomique, Service de Médecine Génomique des Maladies Rares, APHP.Centre, Hôpital Necker-Enfants Malades, Paris, France",
        "Génétique des Troubles du Neurodéveloppement INSERM UMR_1163, Institut Imagine, Université Paris Cité, Paris, France"
      ],
      "name": "Marion Lesieur-Sebellin"
    },
    {
      "affiliations": [
        "Department of Genetics, Division of Genomic Medicine, UC Davis MIND Institute, Sacramento, California, USA",
        "Rady Children’s Institute for Genomic Medicine, San Diego, California, USA"
      ],
      "name": "Kristen Wigby"
    },
    {
      "affiliations": [
        "Service de Génétique Médicale, Institut de Génétique Médicale d’Alsace, Hôpitaux Universitaires de Strasbourg, Strasbourg, France"
      ],
      "name": "Elise Schaefer"
    },
    {
      "affiliations": [
        "Laboratoire de diagnostic génétique, Hôpitaux Universitaires de Strasbourg, Strasbourg, France"
      ],
      "name": "Aurélie Gouronc"
    },
    {
      "affiliations": [
        "Service de Génétique, Hospices Civils de Lyon, Bron Cedex, France",
        "Laboratoire Physiopathologie et Génétique du Neurone et du Muscle, CNRS UMR 5261, Institut NeuroMyoGène, Lyon, France"
      ],
      "name": "Nicolas Chatron"
    },
    {
      "affiliations": [
        "9Service de Neuropédiatrie, Hospices Civils de Lyon, Lyon, France"
      ],
      "name": "Anne-Lise Poulat"
    },
    {
      "affiliations": [
        "Service de Génétique, Hospices Civils de Lyon, Lyon, France",
        "INSERM U1028, CNRS UMR5292, UCBL1, GENDEV Team, Neurosciences Research Center of Lyon, Lyon, France"
      ],
      "name": "Audrey Putoux"
    },
    {
      "affiliations": [
        "Inserm U1245, Univ Rouen Normandie, Normandie Univ, Rouen, France",
        "Department of Genetics and Reference Center for Developmental Disorders, CHU Rouen, Rouen, France"
      ],
      "name": "Alice Goldenberg"
    },
    {
      "affiliations": [
        "Inserm U1245, Univ Rouen Normandie, Normandie Univ, Rouen, France",
        "Department of Genetics and Reference Center for Developmental Disorders, CHU Rouen, Rouen, France"
      ],
      "name": "Mathilde Quibeuf"
    },
    {
      "affiliations": [
        "Inserm U1245, Univ Rouen Normandie, Normandie Univ, Rouen, France",
        "Department of Genetics and Reference Center for Developmental Disorders, CHU Rouen, Rouen, France"
      ],
      "name": "Pascal Chambon"
    },
    {
      "affiliations": [
        "Fédération de Génétique et Médecine Génomique, Service de Médecine Génomique des Maladies Rares, APHP.Centre, Hôpital Necker-Enfants Malades, Paris, France",
        "Molecular Genetics Laboratory, Groupe hospitalier Necker Enfants malades, Assistance publique—Hôpitaux de Paris, Paris, France"
      ],
      "name": "Sophie Rondeau"
    },
    {
      "affiliations": [
        "Fédération de Génétique et Médecine Génomique, Service de Médecine Génomique des Maladies Rares, APHP.Centre, Hôpital Necker-Enfants Malades, Paris, France"
      ],
      "name": "Giulia Barcia"
    },
    {
      "affiliations": [
        "Département de Génétique, Hôpital Robert Debré, Paris, France"
      ],
      "name": "Jonathan Levy"
    },
    {
      "affiliations": [
        "Centre de génétique Humaine, Centre Hospitalier Universitaire, Université de Franche-Comté, Besançon, France",
        "UMR 1231 GAD, Inserm, Université de Bourgogne, Dijon, France"
      ],
      "name": "Juliette Piard"
    },
    {
      "affiliations": [
        "Oncobiologie Génétique Bioinformatique, FHU-TRANSLAD et Institut GIMI, Université de Franche-Comté, CHU Besançon, Besancon, France",
        "INSERM UMR1231 GAD Génétique des Anomalies du Développement, Université de Bourgogne, Dijon, France"
      ],
      "name": "Paul Kuentz"
    },
    {
      "affiliations": [
        "Service de génétique, CRMR anddirares, CHU de Reims, Reims, France",
        "CHU de Nantes, Service de génétique, Nantes, France"
      ],
      "name": "Martine Doco-Fenzy"
    },
    {
      "affiliations": [
        "Service de génétique, CRMR anddirares, CHU de Reims, Reims, France"
      ],
      "name": "Nathalie Bednarek"
    },
    {
      "affiliations": [
        "Service de Génétique Clinique, Hôpital Jeanne de Flandre, Lille, France"
      ],
      "name": "Roseline Caumes"
    },
    {
      "affiliations": [
        "Institut de Génétique Médicale, Hôpital Jeanne de Flandre, Lille, France"
      ],
      "name": "Sonia Bouquillon"
    },
    {
      "affiliations": [
        "Service de Génétique Médicale, CHU Toulouse Purpan, Toulouse, France",
        "ToNIC, INSERM UMR1214, Toulouse, France"
      ],
      "name": "Cedric Le Caignec"
    },
    {
      "affiliations": [
        "Service de Génétique Médicale, CHU Toulouse Purpan, Toulouse, France"
      ],
      "name": "Olivier Patat"
    },
    {
      "affiliations": [
        "Génétique Médicale, Centre de Compétences Anomalies du Développement et Syndromes Malformatifs, Hôpital Carémeau—CHU de Nîmes, Nimes, France"
      ],
      "name": "Philippe Khau Van Kien"
    },
    {
      "affiliations": [
        "UF de Cytogénétique et Génétique Médicale, Hôpital Carémeau, CHU Nîmes, Nîmes, France"
      ],
      "name": "Jean Chiesa"
    },
    {
      "affiliations": [
        "Unité de Génétique Constitutionnelle, Service de Biologie, Centre Hospitalier de Versailles, Le Chesnay, France"
      ],
      "name": "Geoffroy Delplancq"
    },
    {
      "affiliations": [
        "Unité de Génétique Constitutionnelle, Service de Biologie, Centre Hospitalier de Versailles, Le Chesnay, France"
      ],
      "name": "Séverine Bacrot"
    },
    {
      "affiliations": [
        "Unité de Génétique Constitutionnelle, Service de Biologie, Centre Hospitalier de Versailles, Le Chesnay, France"
      ],
      "name": "Sophie Brisset"
    },
    {
      "affiliations": [
        "Service de pédiatrie, Hôpitaux Civils de Colmar, Colmar, France"
      ],
      "name": "Emmanuelle Ginglinger"
    },
    {
      "affiliations": [
        "Génétique des Troubles du Neurodéveloppement INSERM UMR_1163, Institut Imagine, Université Paris Cité, Paris, France"
      ],
      "name": "Vincent Cantagrel"
    },
    {
      "affiliations": [
        "Rady Children’s Institute for Genomic Medicine, San Diego, California, USA"
      ],
      "name": "Jerica Lenberg"
    },
    {
      "affiliations": [
        "Department of Neuroscience, Rady Children’s Institute for Genomic Medicine, San Diego, California, USA",
        "Division of Neurology, Rady Children’s Hospital San Diego, San Diego, California, USA"
      ],
      "name": "Jennifer R Friedman"
    },
    {
      "affiliations": [
        "Fédération de Génétique et Médecine Génomique, Service de Médecine Génomique des Maladies Rares, APHP.Centre, Hôpital Necker-Enfants Malades, Paris, France",
        "Génétique des Troubles du Neurodéveloppement INSERM UMR_1163, Institut Imagine, Université Paris Cité, Paris, France"
      ],
      "name": "Marlène Rio"
    },
    {
      "affiliations": [
        "Laboratoire de diagnostic génétique, Hôpitaux Universitaires de Strasbourg, Strasbourg, France"
      ],
      "name": "Sophie Scheidecker"
    },
    {
      "affiliations": [
        "Fédération de Génétique et Médecine Génomique, Service de Médecine Génomique des Maladies Rares, APHP.Centre, Hôpital Necker-Enfants Malades, Paris, France",
        "Génétique des Troubles du Neurodéveloppement INSERM UMR_1163, Institut Imagine, Université Paris Cité, Paris, France"
      ],
      "name": "Valerie Malan"
    }
  ],
  "title": "ACTB deletions or single-nucleotide loss-of-function variants: expansion and further delineation of the phenotype and review of the literature",
  "uid": "1b55aeae-8d7c-5517-9298-66c6417c0268"
}