ArticleHGG advances2022
Novel diagnostic DNA methylation episignatures expand and refine the epigenetic landscapes of Mendelian disorders.
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Article in HGG advances, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 115 papers, 1 of them a synthesis that pooled it.
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115citing papers in PubMed, 1 pooled it
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Who cites it
115 citing papers in PubMed, 1 synthesis or guideline pooled it, 152 citations in OpenAlex.
- Paediatric DNA methylation profile scores: a systematic review and open-source atlas.EBioMedicine · 2026Pooled it
- Clinical Epigenomics in Rare Diseases: Interpreting DNA Methylation Episignatures.Molecular genetics & genomic medicine · 2026Review
- Nanopore long-read sequencing facilitates accurate diagnosis of KMT2B-related dystonia.Clinical epigenetics · 2026Article
- Biallelic inactivating variants in the chromatin remodeler DMAP1 cause a syndromic neurodevelopmental disorder.The Journal of clinical investigation · 2026Article
- Discovery of a DNA methylation episignature for Weiss-Kruszka syndrome.Human genetics · 2026Article
- Evaluating the Utility of RNAseq in Prenatal Diagnostics: Expression Profiles of Cultured Chorionic Villus and Amniotic Fluid Samples.Prenatal diagnosis · 2026Article
- De novo EHMT2 variants cause an autosomal dominant EHMT2-related Kleefstra syndrome via loss of G9a methyltransferase activity.Nature communications · 2026Article
- Structural variant discovery and diagnostic impact in rare diseases from short-read and long-read sequencing.medRxiv : the preprint server for health sciences · 2026Article
- Population-scale detection of methylation outliers from long-read genome sequencing.medRxiv : the preprint server for health sciences · 2026Article
- Chromatinopathies: clinically overlapping disorders, revealing novel variants and their DNA methylation signatures.Clinical epigenetics · 2026Article
- Identification of an episignature for CHD3-related Snijders Blok-Campeau syndrome reveals heterogeneity in the CHARGE syndrome episignature: towards a better characterisation of chromatinopathies.Genome medicine · 2026Article
- De novo heterozygous variants of the RSF1 gene are responsible for a syndromic neurodevelopmental disorder.European journal of human genetics : EJHG · 2026Article
- Pathogenic variants in the cohesin loader subunit MAU2 underlie a distinct Cornelia de Lange Syndrome subtype.Nature communications · 2026Article
- Clinical,medRxiv : the preprint server for health sciences · 2026Article
- Evaluating DNA methylation episignatures as a first-tier diagnostic test in individuals with suspected genetic disorders.European journal of human genetics : EJHG · 2026Article
- DNA Methylation Episignature as a Novel Diagnostic Tool for Diamond-Blackfan Anemia Syndrome.American journal of hematology · 2026Article
- To sign or not to sign: Is this still the question?European journal of human genetics : EJHG · 2026Article
- Genome-wide methylation detection and episignature analysis using PacBio long-read sequencing.Genome medicine · 2026Article
- De novo variants in KDM2A cause a syndromic neurodevelopmental disorder.American journal of human genetics · 2026Article
- DNA methylation analysis of NOTCH1 variants reveals the first episignature for non-syndromic congenital heart defects.Genome medicine · 2026Article
55 more citing papers are in PubMed but not listed here.
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Authors and funding
87 authors at 20 institutions in 10 countries.
Michael A LevyVerspeeten Clinical Genome Centre; London Health Sciences Centre, London, ON N6A 5W9, Canada.
Haley McConkeyVerspeeten Clinical Genome Centre; London Health Sciences Centre, London, ON N6A 5W9, Canada.
Jennifer KerkhofVerspeeten Clinical Genome Centre; London Health Sciences Centre, London, ON N6A 5W9, Canada.
Mouna Barat-HouariAutoinflammatory and Rare Diseases Unit, Medical Genetic Department for Rare Diseases and Personalized Medicine, CHU Montpellier, Montpellier, France.
Sara BargiacchiMedical Genetics Unit, "A. Meyer" Children's Hospital of Florence, Florence, Italy.
Elisa BiaminoDepartment of Pediatrics, University of Turin, Turin, Italy.
María Palomares BraloInstitute of Medical and Molecular Genetics (INGEMM), Hospital Universitario La Paz, IdiPAZ, CIBERER, ISCIII, Madrid, Spain.
Gerarda CappuccioDepartment of Translational Medicine, Federico II University of Naples, Naples, Italy.
Andrea CiolfiGenetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù, IRCCS, 00146 Rome, Italy.
Angus ClarkeCardiff University School of Medicine, Cardiff, UK.
Barbara R DuPontGreenwood Genetic Center, Greenwood, SC 29646, USA.
Mariet W EltingDepartment of Clinical Genetics, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
Laurence FaivreINSERM-Université de Bourgogne UMR1231 GAD « Génétique Des Anomalies du Développement », FHU-TRANSLAD, UFR Des Sciences de Santé, Dijon, France.
Timothy FeeGreenwood Genetic Center, Greenwood, SC 29646, USA.
Robin S FletcherGreenwood Genetic Center, Greenwood, SC 29646, USA.
Florian CherikGenetic medical center, CHU Clermont Ferrand, France.
Aidin ForoutanDepartment of Pathology and Laboratory Medicine, Western University, London, ON N6A 3K7, Canada.
Michael J FriezGreenwood Genetic Center, Greenwood, SC 29646, USA.
Cristina GervasiniDivision of Medical Genetics, Department of Health Sciences, Università degli Studi di Milano, Milan, Italy.
Sadegheh HaghshenasDepartment of Pathology and Laboratory Medicine, Western University, London, ON N6A 3K7, Canada.
Benjamin A HiltonGreenwood Genetic Center, Greenwood, SC 29646, USA.
Zandra JenkinsDunedin School of Medicine, University of Otago, Dunedin, New Zealand.
Simranpreet KaurBrain and Mitochondrial Research Group, Murdoch Children's Research Institute and Department of Paediatrics, University of Melbourne, Melbourne, Australia.
Suzanne LewisBC Children's and Women's Hospital and Department of Medical Genetics, Faculty of Medicine, University of British Columbia, Vancouver, Canada.
Raymond J LouieGreenwood Genetic Center, Greenwood, SC 29646, USA.
Silvia MaitzClinical Pediatric Genetics Unit, Pediatrics Clinics, MBBM Foundation, Hospital San Gerardo, Monza, Italy.
Donatella MilaniFondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
Angela T MorganMurdoch Children's Research Institute and Department of Paediatrics, University of Melbourne, Melbourne, Australia.
Renske OegemaDepartment of Genetics, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
Elsebet ØstergaardDepartment of Clinical Genetics, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
Nathalie Ruiz PallaresAutoinflammatory and Rare Diseases Unit, Medical Genetic Department for Rare Diseases and Personalized Medicine, CHU Montpellier, Montpellier, France.
Maria PiccioneMedical Genetics Unit Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy.
Simone PizziGenetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù, IRCCS, 00146 Rome, Italy.
Astrid S PlompAmsterdam UMC, University of Amsterdam, Department of Human Genetics, Amsterdam Reproduction and Development Research Institute, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands.
Cathryn PoultonUndiagnosed Diseases Program, Genetic Services of Western Australia, King Edward Memorial Hospital, Perth, Australia.
Jack ReillyDepartment of Pathology and Laboratory Medicine, Western University, London, ON N6A 3K7, Canada.
Raissa RelatorVerspeeten Clinical Genome Centre; London Health Sciences Centre, London, ON N6A 5W9, Canada.
Rocio RiusBrain and Mitochondrial Research Group, Murdoch Children's Research Institute, Melbourne, Australia.
Stephen RobertsonDunedin School of Medicine, University of Otago, Dunedin, New Zealand.
Kathleen RooneyVerspeeten Clinical Genome Centre; London Health Sciences Centre, London, ON N6A 5W9, Canada.
Justine RousseauCHU Sainte-Justine Research Center, University of Montreal, Montreal, QC H3T 1C5, Canada.
Gijs W E SantenDepartment of Clinical Genetics, LUMC, Leiden, the Netherlands.
Fernando Santos-SimarroInstitute of Medical and Molecular Genetics (INGEMM), Hospital Universitario La Paz, IdiPAZ, CIBERER, ISCIII, Madrid, Spain.
Josephine SchijnsDepartment of Pediatrics, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.
Gabriella Maria SqueoDepartment of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Via S. Pansini 5, 80131 Naples, Italy.
Miya St JohnMurdoch Children's Research Institute and Department of Paediatrics, University of Melbourne, Melbourne, Australia.
Christel Thauvin-RobinetINSERM-Université de Bourgogne UMR1231 GAD « Génétique Des Anomalies du Développement », FHU-TRANSLAD, UFR Des Sciences de Santé, Dijon, France.
Giovanna TraficanteMedical Genetics Unit, "A. Meyer" Children's Hospital of Florence, Florence, Italy.
Pleuntje J van der SluijsDepartment of Clinical Genetics, LUMC, Leiden, the Netherlands.
Samantha A VerganoDivision of Medical Genetics and Metabolism, Children's Hospital of The King's Daughters, Norfolk, VA, USA.
Niels VosDepartment of Clinical Genetics, Amsterdam UMC, University of Amsterdam, Amsterdam Reproduction and Development Research Institute, Meibergdreef 9, Amsterdam, the Netherlands.
Kellie K WaldenGreenwood Genetic Center, Greenwood, SC 29646, USA.
Dimitar AzmanovDepartment of Diagnostic Genomics, PathWest Laboratory Medicine, QEII Medical Centre, Perth, Australia.
Tugce BalciDepartment of Pediatrics, Division of Medical Genetics, Western University, London, ON N6A 3K7, Canada.
Siddharth BankaDivision of Evolution, Infection & Genomics, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK.
Jozef GeczSchool of Medicine, Robinson Research Institute, University of Adelaide, Adelaide, SA 5005, Australia.
Peter HennemanAmsterdam UMC, University of Amsterdam, Department of Human Genetics, Amsterdam Reproduction and Development Research Institute, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands.
Jennifer A LeeGreenwood Genetic Center, Greenwood, SC 29646, USA.
Marcel M A M MannensAmsterdam UMC, University of Amsterdam, Department of Human Genetics, Amsterdam Reproduction and Development Research Institute, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands.
Tony RoscioliNeuroscience Research Australia (NeuRA), Sydney, Australia.
Victoria SiuDepartment of Pediatrics, Division of Medical Genetics, Western University, London, ON N6A 3K7, Canada.
David J AmorMurdoch Children's Research Institute and Department of Paediatrics, University of Melbourne, Melbourne, Australia.
Gareth BaynamUndiagnosed Diseases Program, Genetic Services of Western Australia, King Edward Memorial Hospital, Perth, Australia.
Eric G BendPreventionGenetics, Marshfield, WI, USA.
Kym BoycottChildren's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, ON, Canada.
Nicola Brunetti-PierriDepartment of Translational Medicine, Federico II University of Naples, Naples, Italy.
Philippe M CampeauCHU Sainte-Justine Research Center, University of Montreal, Montreal, QC H3T 1C5, Canada.
John ChristodoulouBrain and Mitochondrial Research Group, Murdoch Children's Research Institute and Department of Paediatrics, University of Melbourne, Melbourne, Australia.
David DymentChildren's Hospital of Eastern Ontario, Ottawa, Canada.
Natacha EsberKAT6A Foundation.
Jill A FahrnerDepartments of Genetic Medicine and Pediatrics, Johns Hopkins University, Baltimore, MD 21205, USA.
Mark D FlemingDepartment of Pathology, Boston Children's Hospital, Boston, MA, USA.
David GenevieveMontpellier University, Reference Center for Rare Disease, Medical Genetic Department for Rare Disease and Personalize Medicine, Inserm Unit 1183, CHU Montpellier, Montpellier, France.
Kristin D KerrnohanChildren's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, ON, Canada.
Alisdair McNeillDepartment of Neuroscience, University of Sheffield, Sheffield Children's Hospital NHS Foundation Trust, Sheffield, UK.
Leonie A MenkeDepartment of Pediatrics, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.
Giuseppe MerlaDepartment of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Via S. Pansini 5, 80131 Naples, Italy.
Paolo PronteraMedical Genetics Unit, University of Perugia Hospital SM della Misericordia, Perugia, Italy.
Cheryl Rockman-GreenbergDepartment of Pediatrics and Child Health, Rady Faculty of Health Sciences, University of Manitoba and Program in Genetics and Metabolism, Shared Health MB, Winnipeg, MB, Canada.
Charles SchwartzGreenwood Genetic Center, Greenwood, SC 29646, USA.
Steven A SkinnerGreenwood Genetic Center, Greenwood, SC 29646, USA.
Roger E StevensonGreenwood Genetic Center, Greenwood, SC 29646, USA.
Antonio VitobelloINSERM-Université de Bourgogne UMR1231 GAD « Génétique Des Anomalies du Développement », FHU-TRANSLAD, UFR Des Sciences de Santé, Dijon, France.
Marco TartagliaGenetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù, IRCCS, 00146 Rome, Italy.
Marielle AldersAmsterdam UMC, University of Amsterdam, Department of Human Genetics, Amsterdam Reproduction and Development Research Institute, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands.
Matthew L TedderGreenwood Genetic Center, Greenwood, SC 29646, USA.
Bekim SadikovicVerspeeten Clinical Genome Centre; London Health Sciences Centre, London, ON N6A 5W9, Canada.
Greenwood Genetic Center · USWestern University · CAInserm · FRLondon Health Sciences Centre · CAThe University of Melbourne · AUUniversity of Amsterdam · NLBambino Gesù Children's Hospital · ITHospital Universitario La Paz · ESAmsterdam University Medical Centers · NLCentre Hospitalier Universitaire Sainte-Justine · CAEmma Kinderziekenhuis · NLLeiden University Medical Center · NLMeyer Children's Hospital · ITTelethon Institute Of Genetics And Medicine · ITUniversity of Otago · NZUniversity of Ottawa · CAAzienda Ospedaliera San Gerardo · ITBoston Children's Hospital · USCardiff University · GBCasa Sollievo della Sofferenza · IT
Funding
No grant is acknowledged in the PubMed record.
Abstract
Overlapping clinical phenotypes and an expanding breadth and complexity of genomic associations are a growing challenge in the diagnosis and clinical management of Mendelian disorders. The functional consequences and clinical impacts of genomic variation may involve unique, disorder-specific, genomic DNA methylation episignatures. In this study, we describe 19 novel episignature disorders and compare the findings alongside 38 previously established episignatures for a total of 57 episignatures associated with 65 genetic syndromes. We demonstrate increasing resolution and specificity ranging from protein complex, gene, sub-gene, protein domain, and even single nucleotide-level Mendelian episignatures. We show the power of multiclass modeling to develop highly accurate and disease-specific diagnostic classifiers. This study significantly expands the number and spectrum of disorders with detectable DNA methylation episignatures, improves the clinical diagnostic capabilities through the resolution of unsolved cases and the reclassification of variants of unknown clinical significance, and provides further insight into the molecular etiology of Mendelian conditions.
Indexed as
Clinical diagnosticsDNA methylationEpigeneticsEpisignaturesNeurodevelopmental disorders
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