Identification of a DNA methylation episignature for recurrent constellations of embryonic malformations,American Journal of Human Genetics

当前位置： X-MOL 学术 › Am. J. Hum. Genet. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Identification of a DNA methylation episignature for recurrent constellations of embryonic malformations
American Journal of Human Genetics ( IF 8.1 ) Pub Date : 2024-07-31 , DOI: 10.1016/j.ajhg.2024.07.005
Sadegheh Haghshenas ₁ , Karim Karimi ₁ , Roger E Stevenson ₂ , Michael A Levy ₁ , Raissa Relator ₁ , Jennifer Kerkhof ₁ , Jessica Rzasa ₁ , Haley McConkey ₃ , Carolyn Lauzon-Young ₃ , Tugce B Balci ₄ , Alexandre M White-Brown ₅ , Melissa T Carter ₆ , Julie Richer ₆ , Christine M Armour ₆ , Sarah L Sawyer ₆ , Priya T Bhola ₆ , Matthew L Tedder ₂ , Cindy D Skinner ₂ , Iris A L M van Rooij ₇ , Romy van de Putte ₇ , Ivo de Blaauw ₈ , Rebekka M Koeck ₉ , Alexander Hoischen ₁₀ , Han Brunner ₁₁ , Masoud Zamani Esteki ₉ , Anna Pelet ₁₂ , Stanislas Lyonnet ₁₃ , Jeanne Amiel ₁₃ , Kym M Boycott ₁₄ , Bekim Sadikovic ₃

Affiliation

Verspeeten Clinical Genome Centre, London Health Sciences Centre, London, ON, Canada.
Greenwood Genetic Center, Greenwood, SC 29646, USA.
Verspeeten Clinical Genome Centre, London Health Sciences Centre, London, ON, Canada; Department of Pathology and Laboratory Medicine, Western University, London, ON, Canada.
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.
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.
Department IQ Health, Research Institute for Medical Innovation, Radboud University Medical Center, Nijmegen, the Netherlands.
Department of Surgery-Pediatric Surgery, Radboudumc Amalia Children's Hospital, Radboud University Medical Center, Nijmegen, the Netherlands.
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; 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.
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.
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.
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.
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.

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.

中文翻译：

胚胎畸形复发星座的 DNA 甲基化表观特征鉴定

术语“复发性胚胎畸形星座”(RCEM) 用于描述影响三个或更多身体结构的多种多种畸形关联。这些疾病的原因目前尚不清楚，也没有确定诊断标记。因此，对疑似个体提供明确的诊断具有挑战性。在这项研究中，对从 53 名 RCEM 个体的外周血中获得的 DNA 样本进行了全基因组 DNA 甲基化分析，这些 RCEM 的临床特征被认为是 VACTERL 和/或眼耳椎谱关联。我们在 53 名个体中的 40 名中发现了共同的 DNA 甲基化表观特征。随后，基于 DNA 甲基化表观特征开发了一种灵敏且特异的二元分类器。该分类器可以促进在临床环境中使用 RCEM 表观特征作为诊断生物标志物。该研究还调查了 RCEM DNA 甲基化相对于其他具有已知表观特征的遗传性疾病的功能相关性，强调了 RCEM 病理生理学中涉及的常见基因组调控途径。

更新日期：2024-07-31

点击分享查看原文

点击收藏

阅读更多本刊新发论文本刊介绍/投稿指南