Expanding the Mutational Landscape and Clinical Phenotype of CHD2-Related Encephalopathy
Hwang, Angela (The Francis Crick Institute (Londres, Regne Unit))
Stefani, Stefani (Cyprus Paediatric Neurology Institute (Nicosia, Xipre))
Lau, Tracy (UCL Queen Square Institute of Neurology (Regne Unit))
Scala, Marcello (IRCCS Istituto Giannina Gaslini (Itàlia))
Aynekin, Büşra (UCL Queen Square Institute of Neurology (Regne Unit))
Bernardo, Pia (Santobono-Pausilipon Children's Hospital (Itàlia))
Madia, Francesca (IRCCS Istituto Giannina Gaslini (Gènova, Itàlia))
Bakhtadze, Sophia (Tbilisi State Medical University (Geòrgia))
Kaiyrzhanov, Rauan (UCL Queen Square Institute of Neurology (Regne Unit))
Maroofian, R. (UCL Queen Square Institute of Neurology (Regne Unit))
Zara, Federico (IRCCS Istituto Giannina Gaslini (Itàlia))
Srinivasan, Varunvenkat M. (Indira Gandhi Institute of Child Health (Índia))
Gowda, Vykuntaraju (Indira Gandhi Institute of Child Health (Índia))
Guliyeva, Ulviyya (MediClub Hospital (Azerbaidjan))
Montavont, Alexandra (University Hospital of Lyon (França))
Poulat, Anne-Lise (University Hospital of Lyon (França))
Güleç, Ayten (Erciyes University. Department of Pediatrics (Turquia))
Berger, Colette (University Hospital of Lyon (França))
Ville, Dorothee M. (University Hospital of Lyon (França))
De Bellescize, Julitta (University Hospitals of Lyon. Department of Paediatric Clinical Epileptology (França))
Cabet, Sara (Femme-Mere-Enfant Hospital. Hospices Civils de Lyon. Claude Bernard Lyon 1 University (França))
Wonneberger, Antje (Department of Neuropediatrics. Jena University Hospital)
Schulz, Alexander (MVZ Mitteldeutscher Praxisverbund Humangenetik GmbH)
Rodríguez-Palmero, Agustí (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Chatron, Nicolas (NeuroMyoGene Institute. CNRS UMR 5261-INSERM U1315. Claude Bernard Lyon 1 University)
Lesca, Gaetan (NeuroMyoGene Institute. CNRS UMR 5261-INSERM U1315. Claude Bernard Lyon 1 University)
Per, Hüseyin (Erciyes University)
Goel, Himanshu (University of Newcastle)
Brown, Janis (John Hunter Children's Hospital)
Frey, Tanja (Institute of Medical Genetics)
Steindl, Katharina (Institute of Medical Genetics)
Rauch, Anita (University Children's Hospital Zurich (Zúric, Suïssa))
Severino, Mariasavina (Neuroradiology Unit. IRCCS Giannina Gaslini Institute)
Houlden, Henry (UCL Queen Square Institute of Neurology (Regne Unit))
Nicolaides, Paola (University of Nicosia Medical School)
Striano, Pasquale (Università Degli Studi di Genova)
Efthymiou, Stephanie (UCL Queen Square Institute of Neurology (Regne Unit))

Fecha:	2024
Resumen:	Objectives: To present a case series of novel CHD2 variants in patients presenting with genetic epileptic and developmental encephalopathy. BackgroundCHD2 gene encodes an ATP-dependent enzyme, chromodomain helicase DNA-binding protein 2, involved in chromatin remodeling. Pathogenic variants in CHD2 are linked to early-onset conditions such as developmental and epileptic encephalopathy, drug-resistant epilepsies, and neurodevelopmental disorders. Approximately 225 diagnosed patients from 28 countries exhibit various allelic variants in CHD2, including small intragenic deletions/insertions and missense, nonsense, and splice site variants. ResultsWe present the molecular and clinical characteristics of 17 unreported individuals from 17 families with novel pathogenic or likely pathogenic variants in CHD2. All individuals presented with severe global developmental delay, childhood-onset myoclonic epilepsy, and additional neuropsychiatric features, such as behavioral including autism, ADHD, and hyperactivity. Additional findings include abnormal reflexes, hypotonia and hypertonia, motor impairment, gastrointestinal problems, and kyphoscoliosis. Neuroimaging features included hippocampal signal alterations (4/10), with additional volume loss in 2 cases, inferior vermis hypoplasia (7/10), mild cerebellar atrophy (4/10), and cerebral atrophy (1/10). DiscussionOur study broadens the geographic scope of CHD2-related phenotypes, providing valuable insights into the prevalence and clinical characteristics of this genetic disorder in previously underrepresented populations.
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Publicado en:	Neurology: Genetics, Vol. 10 Núm. 4 (July 2024) , ISSN 2376-7839

DOI: 10.1212/NXG.0000000000200168
PMID: 39035822

8 p, 542.6 KB

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Documentos de investigación > Documentos de los grupos de investigación de la UAB > Centros y grupos de investigación (producción científica) > Ciencias de la salud y biociencias > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP)
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