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Expanding the genetic and clinical spectrum of Tatton-Brown-Rahman syndrome in a series of 24 French patients.
Thomas, Hortense; Alix, Tom; Renard, Émeline; Renaud, Mathilde; Wourms, Justine; Zuily, Stéphane; Leheup, Bruno; Geneviève, David; Dreumont, Natacha; Schmitt, Emmanuelle; Bronner, Myriam; Muller, Marc; Divoux, Marion; Wandzel, Marion; Ravel, Jean-Marie; Dexheimer, Mylène; Becker, Aurélie; Roth, Virginie; Willems, Marjolaine; Coubes, Christine; Vieville, Gaëlle; Devillard, Françoise; Schaefer, Élise; Baer, Sarah; Piton, Amélie; Gérard, Bénédicte; Vincent, Marie; Nizon, Mathilde; Cogné, Benjamin; Ruaud, Lyse; Couque, Nathalie; Putoux, Audrey; Edery, Patrick; Lesca, Gaëtan; Chatron, Nicolas; Till, Marianne; Faivre, Laurence; Tran-Mau-Them, Frédéric; Alessandri, Jean-Luc; Lebrun, Marine; Quélin, Chloé; Odent, Sylvie; Dubourg, Christèle; David, Véronique; Faoucher, Marie; Mignot, Cyril; Keren, Boris; Pisan, Élise; Afenjar, Alexandra; Julia, Sophie.
Afiliação
  • Thomas H; Laboratoire de Génétique, CHRU de Nancy, Vandœuvre-lès-Nancy, France.
  • Alix T; Service de Génétique Clinique, CHRU de Nancy, Nancy, France.
  • Renard É; Laboratoire de Génétique, CHRU de Nancy, Vandœuvre-lès-Nancy, France.
  • Renaud M; INSERM NGERE U1256, Université de Lorraine, Vandœuvre-lès-Nancy, France.
  • Wourms J; INSERM NGERE U1256, Université de Lorraine, Vandœuvre-lès-Nancy, France.
  • Zuily S; Endocrinologie pédiatrique, CHRU de Nancy, Vandœuvre-lès-Nancy, France.
  • Leheup B; Service de Génétique Clinique, CHRU de Nancy, Nancy, France.
  • Geneviève D; INSERM NGERE U1256, Université de Lorraine, Vandœuvre-lès-Nancy, France.
  • Dreumont N; Service de Neurologie, CHRU de Nancy, Nancy, France.
  • Schmitt E; Service de Génétique Clinique, CHRU de Nancy, Nancy, France.
  • Bronner M; Médecine Vasculaire, CHRU de Nancy, Vandœuvre-lès-Nancy, France.
  • Muller M; UMR_S 916 DCAC, INSERM, Vandœuvre-lès-Nancy, France.
  • Divoux M; INSERM NGERE U1256, Université de Lorraine, Vandœuvre-lès-Nancy, France.
  • Wandzel M; Centre de référence anomalies du développement et syndromes malformatifs, Département de Génétique Medicale, Maladies Rares et Médecine Personnalisée, Hôpital Arnaud de Villeneuve, CHU de Montpellier, Montpellier, France.
  • Ravel JM; Inserm U1183, Université Montpellier 1, Faculté de Médecine Montpellier-Nîmes, Montpellier, France.
  • Dexheimer M; INSERM NGERE U1256, Université de Lorraine, Vandœuvre-lès-Nancy, France.
  • Becker A; Neuroradiologie, CHRU de Nancy, Vandœuvre-lès-Nancy, France.
  • Roth V; Laboratoire de Génétique, CHRU de Nancy, Vandœuvre-lès-Nancy, France.
  • Willems M; Laboratoire de Génétique, CHRU de Nancy, Vandœuvre-lès-Nancy, France.
  • Coubes C; Laboratoire de Génétique, CHRU de Nancy, Vandœuvre-lès-Nancy, France.
  • Vieville G; INSERM NGERE U1256, Université de Lorraine, Vandœuvre-lès-Nancy, France.
  • Devillard F; Laboratoire de Génétique, CHRU de Nancy, Vandœuvre-lès-Nancy, France.
  • Schaefer É; Laboratoire de Génétique, CHRU de Nancy, Vandœuvre-lès-Nancy, France.
  • Baer S; INSERM NGERE U1256, Université de Lorraine, Vandœuvre-lès-Nancy, France.
  • Piton A; Laboratoire de Génétique, CHRU de Nancy, Vandœuvre-lès-Nancy, France.
  • Gérard B; Laboratoire de Génétique, CHRU de Nancy, Vandœuvre-lès-Nancy, France.
  • Vincent M; Laboratoire de Génétique, CHRU de Nancy, Vandœuvre-lès-Nancy, France.
  • Nizon M; Centre de référence anomalies du développement et syndromes malformatifs, Département de Génétique Medicale, Maladies Rares et Médecine Personnalisée, Hôpital Arnaud de Villeneuve, CHU de Montpellier, Montpellier, France.
  • Cogné B; Centre de référence anomalies du développement et syndromes malformatifs, Département de Génétique Medicale, Maladies Rares et Médecine Personnalisée, Hôpital Arnaud de Villeneuve, CHU de Montpellier, Montpellier, France.
  • Ruaud L; Département de Génétique et Procréation, Hôpital Couple Enfant, CHU Grenoble Alpes, Grenoble, France.
  • Couque N; Département de Génétique et Procréation, Hôpital Couple Enfant, CHU Grenoble Alpes, Grenoble, France.
  • Putoux A; Service de Génétique médicale, Institut de Génétique Médicale d'Alsace, CHU de Strasbourg, Strasbourg, France.
  • Edery P; Service de Génétique médicale, Institut de Génétique Médicale d'Alsace, CHU de Strasbourg, Strasbourg, France.
  • Lesca G; Service de Génétique médicale, Institut de Génétique Médicale d'Alsace, CHU de Strasbourg, Strasbourg, France.
  • Chatron N; Service de Génétique médicale, Institut de Génétique Médicale d'Alsace, CHU de Strasbourg, Strasbourg, France.
  • Till M; Service de Génétique Médicale, Centre Hospitalier Universitaire de Nantes, Nantes, France.
  • Faivre L; CNRS, INSERM, Institut du thorax, Nantes Université, Nantes, France.
  • Tran-Mau-Them F; Service de Génétique Médicale, Centre Hospitalier Universitaire de Nantes, Nantes, France.
  • Alessandri JL; CNRS, INSERM, Institut du thorax, Nantes Université, Nantes, France.
  • Lebrun M; Service de Génétique Médicale, Centre Hospitalier Universitaire de Nantes, Nantes, France.
  • Quélin C; CNRS, INSERM, Institut du thorax, Nantes Université, Nantes, France.
  • Odent S; Département de Génétique, Hôpital Robert Debré, APHP Nord, Paris, France.
  • Dubourg C; Département de Génétique, Hôpital Robert Debré, APHP Nord, Paris, France.
  • David V; Service de Génétique, Hospices Civils de Lyon, Groupe Hospitalier Est, Bron, France.
  • Faoucher M; CNRS UMR5310, INSERM U1217, Institut NeuroMyoGene PNMG, Université Claude Bernard Lyon 1, Lyon, France.
  • Mignot C; Service de Génétique, Hospices Civils de Lyon, Groupe Hospitalier Est, Bron, France.
  • Keren B; CNRS UMR5310, INSERM U1217, Institut NeuroMyoGene PNMG, Université Claude Bernard Lyon 1, Lyon, France.
  • Pisan É; Service de Génétique, Hospices Civils de Lyon, Groupe Hospitalier Est, Bron, France.
  • Afenjar A; CNRS UMR5310, INSERM U1217, Institut NeuroMyoGene PNMG, Université Claude Bernard Lyon 1, Lyon, France.
  • Julia S; Service de Génétique, Hospices Civils de Lyon, Groupe Hospitalier Est, Bron, France.
J Med Genet ; 61(9): 878-885, 2024 Aug 29.
Article em En | MEDLINE | ID: mdl-38937076
ABSTRACT

BACKGROUND:

Tatton-Brown-Rahman syndrome (TBRS; OMIM 615879), also known as DNA methyltransferase 3 alpha (DNMT3A)-overgrowth syndrome (DOS), was first described by Tatton-Brown in 2014. This syndrome is characterised by overgrowth, intellectual disability and distinctive facial features and is the consequence of germline loss-of-function variants in DNMT3A, which encodes a DNA methyltransferase involved in epigenetic regulation. Somatic variants of DNMT3A are frequently observed in haematological malignancies, including acute myeloid leukaemia (AML). To date, 100 individuals with TBRS with de novo germline variants have been described. We aimed to further characterise this disorder clinically and at the molecular level in a nationwide series of 24 French patients and to investigate the correlation between the severity of intellectual disability and the type of variant.

METHODS:

We collected genetic and medical information from 24 individuals with TBRS using a questionnaire released through the French National AnDDI-Rares Network.

RESULTS:

Here, we describe the first nationwide French cohort of 24 individuals with germline likely pathogenic/pathogenic variants in DNMT3A, including 17 novel variants. We confirmed that the main phenotypic features were intellectual disability (100% of individuals), distinctive facial features (96%) and overgrowth (87%). We highlighted novel clinical features, such as hypertrichosis, and further described the neurological features and EEG results.

CONCLUSION:

This study of a nationwide cohort of individuals with TBRS confirms previously published data and provides additional information and clarifies clinical features to facilitate diagnosis and improve care. This study adds value to the growing body of knowledge on TBRS and broadens its clinical and molecular spectrum.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: DNA (Citosina-5-)-Metiltransferases / DNA Metiltransferase 3A / Deficiência Intelectual Limite: Adolescent / Adult / Child / Child, preschool / Female / Humans / Infant / Male País/Região como assunto: Europa Idioma: En Revista: J Med Genet Ano de publicação: 2024 Tipo de documento: Article País de afiliação: França

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: DNA (Citosina-5-)-Metiltransferases / DNA Metiltransferase 3A / Deficiência Intelectual Limite: Adolescent / Adult / Child / Child, preschool / Female / Humans / Infant / Male País/Região como assunto: Europa Idioma: En Revista: J Med Genet Ano de publicação: 2024 Tipo de documento: Article País de afiliação: França