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Article Dans Une Revue Human Mutation Année : 2022

Functional correlation of genome‐wide DNA methylation profiles in genetic neurodevelopmental disorders

Michael Levy (1) , Raissa Relator (1) , Haley Mcconkey (1) , Erinija Pranckeviciene (2, 3) , Jennifer Kerkhof (1) , Mouna Barat-Houari (4, 5) , Sara Bargiacchi (6) , Elisa Biamino (7) , María Palomares Bralo , Gerarda Cappuccio (8) , Andrea Ciolfi (9) , Angus Clarke (10) , Barbara Dupont , Mariet Elting (11) , Laurence Faivre (12) , Timothy Fee , Marco Ferilli , Robin Fletcher , Florian Cherick , Aidin Foroutan (13, 1) , Michael Friez (14) , Cristina Gervasini (15) , Sadegheh Haghshenas (13, 1) , Benjamin Hilton , Zandra Jenkins , Simranpreet Kaur , Suzanne Lewis (16) , Raymond Louie (14) , Silvia Maitz , Donatella Milani , Angela Morgan , Renske Oegema (17) , Elsebet Østergaard , Nathalie Pallares , Maria Piccione , Astrid Plomp , Cathryn Poulton , Jack Reilly , Rocio Rius , Stephen Robertson , Kathleen Rooney , Justine Rousseau (18) , Gijs Santen , Fernando Santos-Simarro , Josephine Schijns (11) , Gabriella Squeo (8) , Miya St John (19) , Christel Thauvin-Robinet (20) , Giovanna Traficante (21) , Pleuntje van der Sluijs (22) , Samantha Vergano , Niels Vos (11) , Kellie Walden , Dimitar Azmanov , Tugce Balci (13) , Siddharth Banka (23) , Jozef Gecz (24) , Peter Henneman (11) , Jennifer Lee , Marcel Mannens (11) , Tony Roscioli (25) , Victoria Siu (13) , David Amor (19) , Gareth Baynam , Eric Bend , Kym Boycott (2) , Nicola Brunetti-Pierri (26) , Philippe Campeau (18) , Dominique Campion (27) , John Christodoulou (19) , David Dyment (2) , Natacha Esber , Jill Fahrner (28) , Mark Fleming (29) , David Genevieve (30) , Delphine Heron (31) , Thomas Husson (32) , Kristin Kernohan (2) , Alisdair Mcneill (33) , Leonie Menke (11) , Giuseppe Merla (8) , Paolo Prontera (34) , Cheryl Rockman-Greenberg (35) , Charles Schwartz (14) , Steven Skinner (14) , Roger Stevenson (14) , Marie Vincent (36) , Antonio Vitobello (37) , Marco Tartaglia , Marielle Alders (11) , Matthew Tedder (14) , Bekim Sadikovic
1 LHSC - London Health Sciences Center
2 University of Ottawa [Ottawa]
3 OHRI - Ottawa Hospital Research Institute [Ottawa]
4 Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB)
5 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
6 Hospital Universitario La Paz
7 UNITO - Università degli studi di Torino = University of Turin
8 University of Naples Federico II = Università degli studi di Napoli Federico II
9 IRCCS Ospedale Pediatrico Bambino Gesù = Bambino Gesù Children’s Hospital
10 Cardiff University
11 UvA - University of Amsterdam [Amsterdam] = Universiteit van Amsterdam
12 Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon)
13 UWO - University of Western Ontario
14 The Greenwood Genetic Center
15 UNIMI - Università degli Studi di Milano = University of Milan
16 UBC - University of British Columbia
17 UMCU - University Medical Center [Utrecht]
18 UQAM - Université du Québec à Montréal = University of Québec in Montréal
19 University of Melbourne
20 CHU Dijon
21 UniFI - Università degli Studi di Firenze = University of Florence = Université de Florence
22 Universiteit Leiden = Leiden University
23 University of Manchester [Manchester]
24 University of South Australia [Adelaide]
25 Prince of Wales Hospital
26 "Federico II" University of Naples Medical School
27 CHU Rouen
28 JHU - Johns Hopkins University
29 Massachusetts General Hospital [Boston]
30 Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB)
31 AP-HP - Assistance publique - Hôpitaux de Paris (AP-HP)
32 UNIROUEN - Université de Rouen Normandie
33 University of Sheffield [Sheffield]
34 UNIPG - Università degli Studi di Perugia = University of Perugia
35 University of Manitoba [Winnipeg]
36 CHU Nantes - Centre Hospitalier Universitaire de Nantes = Nantes University Hospital
37 CTM - Center for Translational and Molecular medicine [Dijon - UMR1231]
María Palomares Bralo
  • Fonction : Auteur
Angus Clarke
Barbara Dupont
  • Fonction : Auteur
Timothy Fee
  • Fonction : Auteur
Marco Ferilli
  • Fonction : Auteur
Robin Fletcher
  • Fonction : Auteur
Florian Cherick
  • Fonction : Auteur
Benjamin Hilton
  • Fonction : Auteur
Zandra Jenkins
Simranpreet Kaur
  • Fonction : Auteur
Silvia Maitz
  • Fonction : Auteur
Donatella Milani
  • Fonction : Auteur
Angela Morgan
  • Fonction : Auteur
Elsebet Østergaard
  • Fonction : Auteur
Nathalie Pallares
  • Fonction : Auteur
Maria Piccione
  • Fonction : Auteur
Astrid Plomp
  • Fonction : Auteur
Cathryn Poulton
  • Fonction : Auteur
Jack Reilly
  • Fonction : Auteur
Rocio Rius
  • Fonction : Auteur
Stephen Robertson
Kathleen Rooney
  • Fonction : Auteur
Gijs Santen
Fernando Santos-Simarro
  • Fonction : Auteur
Samantha Vergano
  • Fonction : Auteur
Kellie Walden
  • Fonction : Auteur
Dimitar Azmanov
  • Fonction : Auteur
Jozef Gecz
Jennifer Lee
  • Fonction : Auteur
Gareth Baynam
  • Fonction : Auteur
Eric Bend
  • Fonction : Auteur
Kym Boycott
Dominique Campion
  • Fonction : Auteur
John Christodoulou
Natacha Esber
  • Fonction : Auteur
Mark Fleming
Marco Tartaglia
Bekim Sadikovic

Résumé

An expanding range of genetic syndromes are characterized by genome-wide disruptions in DNA methylation profiles referred to as episignatures. Episignatures are distinct, highly sensitive, and specific biomarkers that have recently been applied in clinical diagnosis of genetic syndromes. Episignatures are contained within the broader disorder-specific genome-wide DNA methylation changes, which can share significant overlap among different conditions. In this study, we performed functional genomic assessment and comparison of disorder-specific and overlapping genome-wide DNA methylation changes related to 65 genetic syndromes with previously described episignatures. We demonstrate evidence of disorder-specific and recurring genome-wide differentially methylated probes (DMPs) and regions (DMRs). The overall distribution of DMPs and DMRs across the majority of the neurodevelopmental genetic syndromes analyzed showed substantial enrichment in gene promoters and CpG islands, and under-representation of the more variable intergenic regions. Analysis showed significant enrichment of the DMPs and DMRs in gene pathways and processes related to neurodevelopment, including neurogenesis, synaptic signaling and synaptic transmission. This study expands beyond the diagnostic utility of DNA methylation episignatures by demonstrating correlation between the function of the mutated genes and the consequent genomic DNA methylation profiles as a key functional element in the molecular etiology of genetic neurodevelopmental disorders.

Dates et versions

hal-04521828 , version 1 (26-03-2024)

Identifiants

Citer

Michael Levy, Raissa Relator, Haley Mcconkey, Erinija Pranckeviciene, Jennifer Kerkhof, et al.. Functional correlation of genome‐wide DNA methylation profiles in genetic neurodevelopmental disorders. Human Mutation, 2022, 43 (11), pp.1609-1628. ⟨10.1002/humu.24446⟩. ⟨hal-04521828⟩
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