Novel diagnostic DNA methylation episignatures expand and refine the epigenetic landscapes of Mendelian disorders

MA Levy; H McConkey; J Kerkhof; M Barat-Houari; S Bargiacchi; E Biamino; MP Bralo; G Cappuccio; A Ciolfi; A Clarke; BR DuPont; MW Elting; L Faivre; T Fee; RS Fletcher; F Cherik; A Foroutan; MJ Friez; C Gervasini; S Haghshenas; BA Hilton; Z Jenkins; S Kaur; S Lewis; RJ Louie; S Maitz; D Milani; AT Morgan; R Oegema; E Østergaard; NR Pallares; M Piccione; S Pizzi; AS Plomp; C Poulton; J Reilly; R Relator; R Rius; S Robertson; K Rooney; J Rousseau; GWE Santen; F Santos-Simarro; J Schijns; GM Squeo; M St John; C Thauvin-Robinet; G Traficante; PJ van der Sluijs; SA Vergano; N Vos; KK Walden; D Azmanov; T Balci; S Banka; J Gecz; P Henneman; JA Lee; MMAM Mannens; T Roscioli; V Siu; DJ Amor; G Baynam; EG Bend; K Boycott; N Brunetti-Pierri; PM Campeau; J Christodoulou; D Dyment; N Esber; JA Fahrner; MD Fleming; D Genevieve; KD Kerrnohan; A McNeill; LA Menke; G Merla; P Prontera; C Rockman-Greenberg; C Schwartz; SA Skinner; RE Stevenson; A Vitobello; M Tartaglia; M Alders; ML Tedder; B Sadikovic

Journal article

Novel diagnostic DNA methylation episignatures expand and refine the epigenetic landscapes of Mendelian disorders

MA Levy, H McConkey, J Kerkhof, M Barat-Houari, S Bargiacchi, E Biamino, MP Bralo, G Cappuccio, A Ciolfi, A Clarke, BR DuPont, MW Elting, L Faivre, T Fee, RS Fletcher, F Cherik, A Foroutan, MJ Friez, C Gervasini, S Haghshenas Show all

Human Genetics and Genomics Advances | Published : 2022

DOI: 10.1016/j.xhgg.2021.100075

Download PDF

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 episi..

View full abstract

University of Melbourne Researchers

Simranpreet Kaur Author

Angela Morgan Author

Rocio Rius Author

David Amor Author

Grants

Awarded by Royal Children's Hospital Foundation

Funding Acknowledgements

Funding for this study is provided in part by the London Health Sciences Molecular Diagnostics Development Fund and the Genome Canada Genomic Applications Partnership Program. The research conducted at the Murdoch Children's Research Institute was supported by the Victorian Government's Operational Infrastructure Support Program. The Chair in Genomic Medicine awarded to J.C. is generously supported by The Royal Children's Hospital Foundation. Funding was provided by the Italian Ministry of Health (Ricerca Corrente to A.C.; 5x1000, CCR-201723669081, and RCR-2020-23670068_001 to M.T.) and the Italian Ministry of Research (FOE 2019 to M.T.). The authors wish to acknowledge Care4Rare for providing some of the patient samples. Support for this study is provided in part by the MKHK Association.