Please use this identifier to cite or link to this item:
https://ahro.austin.org.au/austinjspui/handle/1/30173
Title: | CDK13-related disorder: Report of a series of 18 previously unpublished individuals and description of an epigenetic signature. | Austin Authors: | Rouxel, Flavien;Relator, Raissa;Kerkhof, Jennifer;McConkey, Haley;Levy, Michael;Dias, Patricia;Barat-Houari, Mouna;Bednarek, Nathalie;Boute, Odile;Chatron, Nicolas;Cherik, Florian;Delahaye-Duriez, Andrée;Doco-Fenzy, Martine;Faivre, Laurence;Gauthier, Lucas W;Heron, Delphine;Hildebrand, Michael S ;Lesca, Gaëtan;Lespinasse, James;Mazel, Benoit;Menke, Leonie A;Morgan, Angela T;Pinson, Lucile;Quelin, Chloe;Rossi, Massimiliano;Ruiz-Pallares, Nathalie;Tran-Mau-Them, Frederic;Van Kessel, Imke N;Vincent, Marie;Weber, Mathys;Willems, Marjolaine;Leguyader, Gwenael;Sadikovic, Bekim;Genevieve, David | Affiliation: | Epilepsy Research Centre Murdoch Children's Research Institute, Department of Audiology and Speech Pathology, University of Melbourne, Melbourne, Victoria, Australia Department of Audiology and Speech Pathology, Melbourne School of Health Sciences, The University of Melbourne, Parkville, Victoria, Australia Genetics Department, Hospital Center of Lisbon North, ERN ITHACA, Lisbon, Portugal Genetics Department, CHU Reims, Medical school IFR53, EA3801, Reims, France Genetics Department, Guy Fontaine Medical Center, CLAD Nord de France, Jeanne de Flandre Hospital, CHRU Lille, Lille, France Genetics Department, Lyon University Hospital, and Institut NeuroMyoGène, CNRS UMR 5310 - INSERM U1217, Claude Bernard Lyon 1 University, Lyon, France Genetics Department, CHU Clermont-Ferrand, Clermont-Ferrand, France PROTECT, INSERM, Paris Diderot University, Paris, France Genetics Department, University Hospital Pitié-Salpétrière, Paris, France Chromosomic genetic laboratory, CH Général, Chambéry, France Génétique clinique, Département de Génétique Médicale, Maladies Rares et Médecine Personnalisée, CHU Montpellier, Montpellier University, Centre de Référence Anomalies du Développement SOOR, INSERM U1183, ERN ITHACA, Montpellier, France Department of Clinical Genetics, CLAD Ouest, CHU de Rennes, Hôpital Sud, Rennes, France Département de Génétique Médicale, Maladies Rares et Médecine Personnalisée, Génétique des Maladies Rares et Auto-Inflammatoires, CHU Montpellier, Université de Montpellier, Montpellier, France Department of Pediatrics, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, ERN ITHACA, Amsterdam, Netherlands Genetics Department, CHU de Nantes, Nantes, France Centre de Référence Anomalies du Développement et Syndromes Malformatifs, FHU TRANSLAD, CHU Dijon, Dijon, France Genetics Department, CHU de Poitiers, Poitiers University Hospital, Poitiers, France Department of Pathology and Laboratory Medicine, Western University, London, Ontario, Canada The Archie & Irene Verspeeten Clinical Genome Centre, London Health Sciences Centre, London, Ontario, Canada Paris 13 University, Sorbonne Paris Cité, UFR SMBH Bobigny Genetics Department, Referral Centre for Developmental Abnormalities, Lyon University Hospital Lyon, France Genetics of Developmental Disorders, INSERM - Bourgogne Franche-Comté University, UMR 1231 GAD Team, Dijon, France INSERM U1028, CNRS UMR5292, Lyon Neuroscience Research Centre, GENDEV Team, Claude Bernard Lyon 1 University, Lyon, France Functional Unit 6254 Innovation in Genomic Diagnosis of Rare Diseases, CHU Dijon Bourgogne, Dijon, France |
Issue Date: | May-2022 | Date: | 2022-01-19 | Publication information: | Genetics in Medicine 2022; 24(5): 1096-1107 | Abstract: | Rare genetic variants in CDK13 are responsible for CDK13-related disorder (CDK13-RD), with main clinical features being developmental delay or intellectual disability, facial features, behavioral problems, congenital heart defect, and seizures. In this paper, we report 18 novel individuals with CDK13-RD and provide characterization of genome-wide DNA methylation. We obtained clinical phenotype and neuropsychological data for 18 and 10 individuals, respectively, and compared this series with the literature. We also compared peripheral blood DNA methylation profiles in individuals with CDK13-RD, controls, and other neurodevelopmental disorders episignatures. Finally, we developed a support vector machine-based classifier distinguishing CDK13-RD and non-CDK13-RD samples. We reported health and developmental parameters, clinical data, and neuropsychological profile of individuals with CDK13-RD. Genome-wide differential methylation analysis revealed a global hypomethylated profile in individuals with CDK13-RD in a highly sensitive and specific model that could aid in reclassifying variants of uncertain significance. We describe the novel features such as anxiety disorder, cryptorchidism, and disrupted sleep in CDK13-RD. We define a CDK13-RD DNA methylation episignature as a diagnostic tool and a defining functional feature of the evolving clinical presentation of this disorder. We also show overlap of the CDK13 DNA methylation profile in an individual with a functionally and clinically related CCNK-related disorder. | URI: | https://ahro.austin.org.au/austinjspui/handle/1/30173 | DOI: | 10.1016/j.gim.2021.12.016 | ORCID: | 0000-0003-2739-0515 | Journal: | Genetics in Medicine : Official Journal of the American College of Medical Genetics | PubMed URL: | 35063350 | PubMed URL: | https://pubmed.ncbi.nlm.nih.gov/35063350/ | Type: | Journal Article | Subjects: | CDK13 CHDFIDD Clinical Epigenetic Signature |
Appears in Collections: | Journal articles |
Show full item record
Items in AHRO are protected by copyright, with all rights reserved, unless otherwise indicated.