دورية أكاديمية
The different clinical facets of SYN1 -related neurodevelopmental disorders.
| العنوان: | The different clinical facets of SYN1 -related neurodevelopmental disorders. |
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| المؤلفون: | Parenti I; Institute of Human Genetics, University Hospital Essen, University Duisburg-Essen, Essen, Germany., Leitão E; Institute of Human Genetics, University Hospital Essen, University Duisburg-Essen, Essen, Germany., Kuechler A; Institute of Human Genetics, University Hospital Essen, University Duisburg-Essen, Essen, Germany., Villard L; INSERM, MMG, Faculté de Médecine, Aix-Marseille University, Marseille, France.; Département de Génétique Médicale, APHM, Hôpital d'Enfants de La Timone, Marseille, France., Goizet C; Service de Génétique Médicale, Bordeaux, France.; Centre de Référence Maladies Rares Neurogénétique, Service de Génétique Médicale, Bordeaux, France.; NRGEN Team, INCIA, CNRS UMR 5287, University of Bordeaux, Bordeaux, France., Courdier C; Service de Génétique Médicale, Bordeaux, France.; Centre de Référence Maladies Rares Neurogénétique, Service de Génétique Médicale, Bordeaux, France.; NRGEN Team, INCIA, CNRS UMR 5287, University of Bordeaux, Bordeaux, France., Bayat A; Institute for Regional Health Services, University of Southern Denmark, Odense, Denmark.; Department of Epilepsy Genetics and Personalized Medicine, Danish Epilepsy Center, Dianalund, Denmark.; Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark., Rossi A; Department of Epilepsy Genetics and Personalized Medicine, Danish Epilepsy Center, Dianalund, Denmark.; Pediatric Clinic, IRCCS Policlinico San Matteo Foundation, University of Pavia, Pavia, Italy., Julia S; Service de Génétique Médicale, Pôle de Biologie, CHU de Toulouse - Hôpital Purpan, Toulouse, France., Bruel AL; Unité Fonctionnelle Innovation en Diagnostic Génomique des Maladies Rares, FHU-TRANSLAD, CHU Dijon Bourgogne, Dijon, France.; UMR1231 GAD, Inserm - Université Bourgogne-Franche Comté, Dijon, France., Tran Mau-Them F; Unité Fonctionnelle Innovation en Diagnostic Génomique des Maladies Rares, FHU-TRANSLAD, CHU Dijon Bourgogne, Dijon, France.; UMR1231 GAD, Inserm - Université Bourgogne-Franche Comté, Dijon, France., Nambot S; UMR1231 GAD, Inserm - Université Bourgogne-Franche Comté, Dijon, France., Lehalle D; Unité Fonctionnelle Innovation en Diagnostic Génomique des Maladies Rares, FHU-TRANSLAD, CHU Dijon Bourgogne, Dijon, France.; UMR1231 GAD, Inserm - Université Bourgogne-Franche Comté, Dijon, France., Willems M; Department of Medical Genetics, Rare diseases and Personalized Medicine, CHU Montpellier, University of Montpellier, Montpellier, France.; Inserm U1298, INM, CHU Montpellier, University of Montpellier, Montpellier, France., Lespinasse J; Service de Cytogenetique, Centre Hospitalier de Chambéry, Chambéry, France., Ghoumid J; Univ. Lille, ULR7364 RADEME, Lille, France.; CHU Lille, Clinique de Génétique, Guy Fontaine, Lille, France., Caumes R; Univ. Lille, ULR7364 RADEME, Lille, France.; CHU Lille, Clinique de Génétique, Guy Fontaine, Lille, France., Smol T; Univ. Lille, ULR7364 RADEME, Lille, France.; CHU Lille, Institut de Génétique Médicale, Lille, France., El Chehadeh S; Service de Génétique Médicale, Institut de Génétique Médicale d'Alsace (IGMA), Hôpitaux Universitaires de Strasbourg, Hôpital de Hautepierre, Strasbourg, France., Schaefer E; Service de Génétique Médicale, Institut de Génétique Médicale d'Alsace (IGMA), Hôpitaux Universitaires de Strasbourg, Hôpital de Hautepierre, Strasbourg, France., Abi-Warde MT; Département de NeuroPédiatrie, Hôpitaux Universitaires de Strasbourg, Strasbourg, France., Keren B; APHP, Département de Génétique, UF de Génomique du Développement, Département de Génétique, Groupe Hospitalier Pitié-Salpêtrière, Sorbonne Université, Paris, France., Afenjar A; Département de Génétique, Centre de Référence déficiences Intellectuelles de Causes Rares, APHP, Hôpital Armand Trousseau, Sorbonne Université, Paris, France., Tabet AC; APHP, Département de Génétique, Hôpital Robert-Debré, Paris, France., Levy J; APHP, Département de Génétique, Hôpital Robert-Debré, Paris, France., Maruani A; Department of Child and Adolescent Psychiatry, Robert Debré Hospital, APHP, Paris, France., Aledo-Serrano Á; Epilepsy and Neurogenetics Program, Neurology Department, Ruber Internacional Hospital, Madrid, Spain., Garming W; Sozialpädiatrisches Zentrum, Kinder-und Jugendklinik Gelsenkirchen, Gelsenkirchen, Germany., Milleret-Pignot C; Service de Pédiatrie, CH de Mâcon, Mâcon, France., Chassevent A; Department of Neurogenetics, Kennedy Krieger Institute, Baltimore, MD, United States., Koopmans M; Department of Genetics, Utrecht University Medical Center, Utrecht, Netherlands., Verbeek NE; Department of Genetics, Utrecht University Medical Center, Utrecht, Netherlands., Person R; GeneDx, Gaithersburg, MD, United States., Belles R; Medical Genetics, Geisinger Medical Center, Danville, PA, United States., Bellus G; Medical Genetics, Geisinger Medical Center, Danville, PA, United States., Salbert BA; Medical Genetics, Geisinger Medical Center, Danville, PA, United States., Kaiser FJ; Institute of Human Genetics, University Hospital Essen, University Duisburg-Essen, Essen, Germany.; Essener Zentrum für Seltene Erkrankungen (EZSE), Universitätsklinikum Essen, Essen, Germany., Mazzola L; Department of Neurology, University Hospital, Lyon Neuroscience Research Center (CRNL), INSERM U1028, CNRS UMR5292, Lyon, France.; Department of Neurology, University Hospital, Saint-Etienne, France., Convers P; Department of Neurology, University Hospital, Lyon Neuroscience Research Center (CRNL), INSERM U1028, CNRS UMR5292, Lyon, France.; Department of Neurology, University Hospital, Saint-Etienne, France., Perrin L; Department of Paediatric Physical Medicine and Rehabilitation, CHU Saint-Étienne, Hôpital Bellevue, Rhône-Alpes Reference Centre for Neuromuscular Diseases, Saint-Étienne, France., Piton A; Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch, France.; Centre National de la Recherche Scientifique, UMR7104, Illkirch, France.; Institut National de la Santé et de la Recherche Médicale, U964, Illkirch, France.; Université de Strasbourg, Illkirch, France., Wiegand G; Division of Pediatric Neurology, Department of Pediatrics, Asklepios Klinik Nord-Heidberg, Hamburg, Germany.; Department of Pediatric and Adolescent Medicine II (Neuropediatrics, Social Pediatrics), University Medical Centre Schleswig-Holstein, Kiel, Germany., Accogli A; Department of Specialized Medicine, Division of Medical Genetics, McGill University Health Centre, Montreal, Qc, Canada.; Department of Human Genetics, Faculty of Medicine, McGill University, Montreal, Qc, Canada., Brancati F; Department of Life, Human Genetics, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy.; IRCCS San Raffaele Roma, Rome, Italy., Benfenati F; Center for Synaptic Neuroscience and Technology, Istituto Italiano di Tecnologia, Geneva, Italy.; IRCCS Ospedale Policlinico San Martino, Geneva, Italy., Chatron N; Service de Genetique, Hospices Civils de Lyon, Bron, France.; Institute NeuroMyoGène, Laboratoire Physiopathologie et Génétique du Neurone et du Muscle, CNRS UMR 5261 -INSERM U1315, Université de Lyon - Université Claude Bernard Lyon 1, Lyon, France., Lewis-Smith D; Translational and Clinical Research Institute, Newcastle University, Newcastle Upon Tyne, United Kingdom.; Department of Clinical Neurosciences, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle Upon Tyne, United Kingdom., Thomas RH; Translational and Clinical Research Institute, Newcastle University, Newcastle Upon Tyne, United Kingdom.; Department of Clinical Neurosciences, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle Upon Tyne, United Kingdom., Zara F; IRCCS G. Gaslini, Genova, Italy.; Department of Neurology, Rehabilitation, Ophtalmology, Genetics, Maternal and Child Health, University of Genova, Genova, Italy., Striano P; IRCCS G. Gaslini, Genova, Italy.; Department of Neurology, Rehabilitation, Ophtalmology, Genetics, Maternal and Child Health, University of Genova, Genova, Italy., Lesca G; Service de Genetique, Hospices Civils de Lyon, Bron, France.; Institute NeuroMyoGène, Laboratoire Physiopathologie et Génétique du Neurone et du Muscle, CNRS UMR 5261 -INSERM U1315, Université de Lyon - Université Claude Bernard Lyon 1, Lyon, France., Depienne C; Institute of Human Genetics, University Hospital Essen, University Duisburg-Essen, Essen, Germany. |
| المصدر: | Frontiers in cell and developmental biology [Front Cell Dev Biol] 2022 Dec 08; Vol. 10, pp. 1019715. Date of Electronic Publication: 2022 Dec 08 (Print Publication: 2022). |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Frontiers Media S.A Country of Publication: Switzerland NLM ID: 101630250 Publication Model: eCollection Cited Medium: Print ISSN: 2296-634X (Print) Linking ISSN: 2296634X NLM ISO Abbreviation: Front Cell Dev Biol Subsets: PubMed not MEDLINE |
| أسماء مطبوعة: | Original Publication: Lausanne : Frontiers Media S.A., [2013]- |
| مستخلص: | Synapsin-I (SYN1) is a presynaptic phosphoprotein crucial for synaptogenesis and synaptic plasticity. Pathogenic SYN1 variants are associated with variable X-linked neurodevelopmental disorders mainly affecting males. In this study, we expand on the clinical and molecular spectrum of the SYN1 -related neurodevelopmental disorders by describing 31 novel individuals harboring 22 different SYN1 variants. We analyzed newly identified as well as previously reported individuals in order to define the frequency of key features associated with these disorders. Specifically, behavioral disturbances such as autism spectrum disorder or attention deficit hyperactivity disorder are observed in 91% of the individuals, epilepsy in 82%, intellectual disability in 77%, and developmental delay in 70%. Seizure types mainly include tonic-clonic or focal seizures with impaired awareness. The presence of reflex seizures is one of the most representative clinical manifestations related to SYN1 . In more than half of the cases, seizures are triggered by contact with water, but other triggers are also frequently reported, including rubbing with a towel, fever, toothbrushing, fingernail clipping, falling asleep, and watching others showering or bathing. We additionally describe hyperpnea, emotion, lighting, using a stroboscope, digestive troubles, and defecation as possible triggers in individuals with SYN1 variants. The molecular spectrum of SYN1 variants is broad and encompasses truncating variants (frameshift, nonsense, splicing and start-loss variants) as well as non-truncating variants (missense substitutions and in-frame duplications). Genotype-phenotype correlation revealed that epileptic phenotypes are enriched in individuals with truncating variants. Furthermore, we could show for the first time that individuals with early seizures onset tend to present with severe-to-profound intellectual disability, hence highlighting the existence of an association between early seizure onset and more severe impairment of cognitive functions. Altogether, we present a detailed clinical description of the largest series of individuals with SYN1 variants reported so far and provide the first genotype-phenotype correlations for this gene. A timely molecular diagnosis and genetic counseling are cardinal for appropriate patient management and treatment. Competing Interests: Author RP was employed by GeneDx. RT reports Honoraria from Arvelle/Angelini, Bial, Eisai, GW Pharma/Jazz, Sanofi, UCB Pharma and Zogenix, and unrestricted funding support from Arvelle/Angelini and UNEEG. PS has served on a scientific advisory board for the Italian Agency of the Drug (AIFA); has received honoraria from GW pharma, Kolfarma s.r.l., Proveca Pharma Ltd, and Eisai Inc.; and has received research support from the Italian Ministry of Health (Ricerca Corrente 2022) and Fondazione San Paolo. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Parenti, Leitão, Kuechler, Villard, Goizet, Courdier, Bayat, Rossi, Julia, Bruel, Tran Mau-Them, Nambot, Lehalle, Willems, Lespinasse, Ghoumid, Caumes, Smol, El Chehadeh, Schaefer, Abi-Warde, Keren, Afenjar, Tabet, Levy, Maruani, Aledo-Serrano, Garming, Milleret-Pignot, Chassevent, Koopmans, Verbeek, Person, Belles, Bellus, Salbert, Kaiser, Mazzola, Convers, Perrin, Piton, Wiegand, Accogli, Brancati, Benfenati, Chatron, Lewis-Smith, Thomas, Zara, Striano, Lesca and Depienne.) |
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| فهرسة مساهمة: | Keywords: SYN1; autism spectrum disorders; genotype-phenotype correlation; neurodevelopmental disorders; reflex epilepsy; synapsins |
| تواريخ الأحداث: | Date Created: 20221226 Latest Revision: 20230103 |
| رمز التحديث: | 20240628 |
| مُعرف محوري في PubMed: | PMC9773998 |
| DOI: | 10.3389/fcell.2022.1019715 |
| PMID: | 36568968 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 2296-634X |
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| DOI: | 10.3389/fcell.2022.1019715 |