Identification of a DNA methylation episignature for recurrent constellations of embryonic malformations.

DNA methylation OAV VACTERL epigenetics episignature recurrent constellations of embryonic malformations

Journal

American journal of human genetics
ISSN: 1537-6605
Titre abrégé: Am J Hum Genet
Pays: United States
ID NLM: 0370475

Informations de publication

Date de publication:
24 Jul 2024
Historique:
received: 27 02 2024
revised: 27 06 2024
accepted: 03 07 2024
medline: 2 8 2024
pubmed: 2 8 2024
entrez: 1 8 2024
Statut: aheadofprint

Résumé

The term "recurrent constellations of embryonic malformations" (RCEM) is used to describe a number of multiple malformation associations that affect three or more body structures. The causes of these disorders are currently unknown, and no diagnostic marker has been identified. Consequently, providing a definitive diagnosis in suspected individuals is challenging. In this study, genome-wide DNA methylation analysis was conducted on DNA samples obtained from the peripheral blood of 53 individuals with RCEM characterized by clinical features recognized as VACTERL and/or oculoauriculovertebral spectrum association. We identified a common DNA methylation episignature in 40 out of the 53 individuals. Subsequently, a sensitive and specific binary classifier was developed based on the DNA methylation episignature. This classifier can facilitate the use of RCEM episignature as a diagnostic biomarker in a clinical setting. The study also investigated the functional correlation of RCEM DNA methylation relative to other genetic disorders with known episignatures, highlighting the common genomic regulatory pathways involved in the pathophysiology of RCEM.

Identifiants

DOI: 10.1016/j.ajhg.2024.07.005 PMID: 39089258
pubmed: 39089258
pii: S0002-9297(24)00247-7
doi: 10.1016/j.ajhg.2024.07.005
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2024 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests B.S. is a shareholder in EpiSign Inc. involved in commercial uses of EpiSign technology.

Auteurs

Sadegheh Haghshenas (S)

Verspeeten Clinical Genome Centre, London Health Sciences Centre, London, ON, Canada.

Karim Karimi (K)

Verspeeten Clinical Genome Centre, London Health Sciences Centre, London, ON, Canada.

Roger E Stevenson (RE)

Greenwood Genetic Center, Greenwood, SC 29646, USA.

Michael A Levy (MA)

Verspeeten Clinical Genome Centre, London Health Sciences Centre, London, ON, Canada.

Raissa Relator (R)

Verspeeten Clinical Genome Centre, London Health Sciences Centre, London, ON, Canada.

Jennifer Kerkhof (J)

Verspeeten Clinical Genome Centre, London Health Sciences Centre, London, ON, Canada.

Jessica Rzasa (J)

Verspeeten Clinical Genome Centre, London Health Sciences Centre, London, ON, Canada.

Haley McConkey (H)

Verspeeten Clinical Genome Centre, London Health Sciences Centre, London, ON, Canada; Department of Pathology and Laboratory Medicine, Western University, London, ON, Canada.

Carolyn Lauzon-Young (C)

Verspeeten Clinical Genome Centre, London Health Sciences Centre, London, ON, Canada; Department of Pathology and Laboratory Medicine, Western University, London, ON, Canada.

Tugce B Balci (TB)

Department of Pediatrics, Division of Medical Genetics, Western University, London, ON, Canada; Medical Genetics Program of Southwestern Ontario, London Health Sciences Centre and Children's Health Research Institute, London, ON, Canada.

Alexandre M White-Brown (AM)

Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, ON, Canada.

Melissa T Carter (MT)

Department of Genetics, Children's Hospital of Eastern Ontario, Ottawa, ON, Canada.

Julie Richer (J)

Department of Genetics, Children's Hospital of Eastern Ontario, Ottawa, ON, Canada.

Christine M Armour (CM)

Department of Genetics, Children's Hospital of Eastern Ontario, Ottawa, ON, Canada.

Sarah L Sawyer (SL)

Department of Genetics, Children's Hospital of Eastern Ontario, Ottawa, ON, Canada.

Priya T Bhola (PT)

Department of Genetics, Children's Hospital of Eastern Ontario, Ottawa, ON, Canada.

Matthew L Tedder (ML)

Greenwood Genetic Center, Greenwood, SC 29646, USA.

Cindy D Skinner (CD)

Greenwood Genetic Center, Greenwood, SC 29646, USA.

Iris A L M van Rooij (IALM)

Department IQ Health, Research Institute for Medical Innovation, Radboud University Medical Center, Nijmegen, the Netherlands.

Romy van de Putte (R)

Department IQ Health, Research Institute for Medical Innovation, Radboud University Medical Center, Nijmegen, the Netherlands.

Ivo de Blaauw (I)

Department of Surgery-Pediatric Surgery, Radboudumc Amalia Children's Hospital, Radboud University Medical Center, Nijmegen, the Netherlands.

Rebekka M Koeck (RM)

Department of Clinical Genetics, Maastricht University Medical Centre+, Maastricht, the Netherlands; Department of Genetics and Cell Biology, GROW School for Oncology and Reproduction, Maastricht University, Maastricht, the Netherlands.

Alexander Hoischen (A)

Department of Human Genetics and Donders Center for Neuroscience, Radboud University Medical Center, Nijmegen, the Netherlands; Center for Infectious Diseases (RCI), Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands; Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands; Radboud Expertise Center for Immunodeficiency and Autoinflammation and Radboud Center for Infectious Disease (RCI), Radboud University Medical Center, Nijmegen, the Netherlands.

Han Brunner (H)

Department of Clinical Genetics, Maastricht University Medical Centre+, Maastricht, the Netherlands; Department of Genetics and Cell Biology, GROW School for Oncology and Reproduction, Maastricht University, Maastricht, the Netherlands; Department of Human Genetics and Donders Center for Neuroscience, Radboud University Medical Center, Nijmegen, the Netherlands.

Masoud Zamani Esteki (MZ)

Department of Clinical Genetics, Maastricht University Medical Centre+, Maastricht, the Netherlands; Department of Genetics and Cell Biology, GROW School for Oncology and Reproduction, Maastricht University, Maastricht, the Netherlands.

Anna Pelet (A)

Laboratory of Embryology and Genetics of Human Malformations, Institut National de La Santé et de La Recherche Médicale (INSERM) UMR 1163, Institut Imagine and Université Paris Cité, Paris, France.

Stanislas Lyonnet (S)

Laboratory of Embryology and Genetics of Human Malformations, Institut National de La Santé et de La Recherche Médicale (INSERM) UMR 1163, Institut Imagine and Université Paris Cité, Paris, France; Service de Médecine Génomique des Maladies Rares, Hôpital Necker-Enfants Malades, AP-HP, Paris, France.

Jeanne Amiel (J)

Laboratory of Embryology and Genetics of Human Malformations, Institut National de La Santé et de La Recherche Médicale (INSERM) UMR 1163, Institut Imagine and Université Paris Cité, Paris, France; Service de Médecine Génomique des Maladies Rares, Hôpital Necker-Enfants Malades, AP-HP, Paris, France.

Kym M Boycott (KM)

Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, ON, Canada; Department of Genetics, Children's Hospital of Eastern Ontario, Ottawa, ON, Canada. Electronic address: kboycott@cheo.on.ca.

Bekim Sadikovic (B)

Verspeeten Clinical Genome Centre, London Health Sciences Centre, London, ON, Canada; Department of Pathology and Laboratory Medicine, Western University, London, ON, Canada. Electronic address: bekim.sadikovic@lhsc.on.ca.

Classifications MeSH