Bainbridge-Ropers syndrome caused by loss-of-function variants in ASXL3: a recognizable condition

Autor: Thomas Wieland, Ute Grasshoff, Jean-Baptiste Rivière, André Reis, Ingrid Bader, Holger Prokisch, Tim M. Strom, Ute Hehr, Olaf Rittinger, Elisabeth Graf, Johannes Koch, Ulrike Hüffmeier, Hermann-Josef Lüdecke, Hartmut Engels, Laurence Faivre, Alma Kuechler, Dagmar Wieczorek, Stefanie Beck-Woedl, Tiffany Busa, Wolfgang Sperl, Tobias B. Haack, Johanna Christina Czeschik
Přispěvatelé: Institut für Humangenetik [Essen], Universität Duisburg-Essen = University of Duisburg-Essen [Essen]-Universitätsklinikum Essen [Universität Duisburg-Essen] (Uniklinik Essen), Institute of Human Genetics, Helmholtz Zentrum München = German Research Center for Environmental Health, Institut für Medizinische Genetik und Angewandte Genomik, Universitäts Klinikum Tübingen, Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Génétique Médicale et Génomique Fonctionnelle (GMGF), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Laboratoire de cytogénétique (CHU de Dijon), Paracelsus Medizinische Privatuniversität = Paracelsus Medical University (PMU), Zentrum für Humangenetik, University Hospital Regensburg, Rheinische Friedrich-Wilhelms-Universität Bonn, Interdisciplinary Center for Clinical Research (laboratory rotation) of the Clinical Center Erlangen of the Friedrich-Alexander-Universitat Erlangen-Nurnberg German Ministry of Research and Education as part of the National Genome Research Network 01GS08164 01GS08167 01GS08163 German Network for Mitochondrial Disorders (mitoNET) 01GM1113 E-Rare project GENOMIT 01GM1207 uniorverbund in der Systemmedizin 'mitOmics' FKZ 01ZX1405C PARI Marfanoid habitus and intellectual deficiency (Regional Council of Burgundy, France) PARI Marfanoid habitus and intellectual deficiency (Dijon University Hospital, France), Universität Duisburg-Essen [Essen]-Universitätsklinikum Essen [Universität Duisburg-Essen] (Uniklinik Essen), Helmholtz-Zentrum München (HZM), Universität Duisburg-Essen [Essen]-Universitätsklinikum Essen [Universität Duisburg-Essen] ( Uniklinik Essen ), Helmholtz-Zentrum München ( HZM ), Friedrich Alexander University [Erlangen-Nürnberg], Génétique Médicale et Génomique Fonctionnelle ( GMGF ), Aix Marseille Université ( AMU ) -Assistance Publique - Hôpitaux de Marseille ( APHM ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Lipides - Nutrition - Cancer [Dijon - U1231] ( LNC ), Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Paracelsus Medical University, Friedrich-Alexander Universität Erlangen-Nürnberg ( FAU ), Bonn Universität [Bonn], Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM)
Jazyk: angličtina
Rok vydání: 2017
Předmět:
Zdroj: European Journal of Human Genetics
European Journal of Human Genetics, 2017, 25 (2), pp.183-191. ⟨10.1038/ejhg.2016.165⟩
European Journal of Human Genetics, Nature Publishing Group, 2017, 25 (2), pp.183-191. ⟨10.1038/ejhg.2016.165⟩
European Journal of Human Genetics, Nature Publishing Group, 2017, 25 (2), pp.183-191. 〈https://www.nature.com/npg_/contact/offices.html〉. 〈10.1038/ejhg.2016.165〉
Eur. J. Hum. Genet. 25, 183-191 (2017)
ISSN: 1018-4813
1476-5438
Popis: International audience; Truncating ASXL3 mutations were first identified in 2013 by Bainbridge et al. as a cause of syndromic intellectual disability in four children with similar phenotypes using whole-exome sequencing. The clinical features - postulated by Bainbridge et al. to be overlapping with Bohring-Opitz syndrome - were developmental delay, severe feeding difficulties, failure to thrive and neurological abnormalities. This condition was included in OMIM as 'Bainbridge-Ropers syndrome' (BRPS, #615485). To date, a total of nine individuals with BRPS have been published in the literature in four reports (Bainbridge et al., Dinwiddie et al, Srivastava et al. and Hori et al.). In this report, we describe six unrelated patients with newly diagnosed heterozygous de novo loss-of-function variants in ASXL3 and concordant clinical features: severe muscular hypotonia with feeding difficulties in infancy, significant motor delay, profound speech impairment, intellectual disability and a characteristic craniofacial phenotype (long face, arched eyebrows with mild synophrys, downslanting palpebral fissures, prominent columella, small alae nasi, high, narrow palate and relatively little facial expression). The majority of key features characteristic for Bohring-Opitz syndrome were absent in our patients (eg, the typical posture of arms, intrauterine growth retardation, microcephaly, trigonocephaly, typical facial gestalt with nevus flammeus of the forehead and exophthalmos). Therefore we emphasize that BRPS syndrome, caused by ASXL3 loss-of-function variants, is a clinically distinct intellectual disability syndrome with a recognizable phenotype distinguishable from that of Bohring-Opitz syndrome.
Databáze: OpenAIRE
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