DNA methylation episignatures are sensitive and specific biomarkers for detection of patients with KAT6A / KAT6B variants.

Autor: Vos N; Department of Human Genetics, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105, AZ, Amsterdam, The Netherlands., Reilly J; Department of Pathology & Laboratory Medicine, Western University, London, ON, N6A 5C1, Canada., Elting MW; Department of Human Genetics, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105, AZ, Amsterdam, The Netherlands., Campeau PM; Department of Pediatrics, Sainte-Justine UHC & University of Montreal, Montreal, QC, H3T 1C5, Canada., Coman D; Department of Metabolic Medicine, Queensland Children's Hospital, South Brisbane, QLD 4101, Australia.; School of Medicine, University of Queensland, Brisbane, QLD 4072, Australia., Stark Z; Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Parkville, Victoria, 3052, Australia.; Department of Paediatrics, University of Melbourne, Grattan Street, Parkville, Victoria, 3010, Australia., Tan TY; Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Parkville, Victoria, 3052, Australia.; Department of Paediatrics, University of Melbourne, Grattan Street, Parkville, Victoria, 3010, Australia., Amor DJ; Murdoch Children's Research Institute, Royal Children's Hospital, Flemington Rd, Parkville VIC, 3052, Australia.; University of Melbourne Department of Pediatrics, Parkville, Victoria, 3010, Australia., Kaur S; Murdoch Children's Research Institute, Royal Children's Hospital, Flemington Rd, Parkville VIC, 3052, Australia.; University of Melbourne Department of Pediatrics, Parkville, Victoria, 3010, Australia., StJohn M; Murdoch Children's Research Institute, Royal Children's Hospital, Flemington Rd, Parkville VIC, 3052, Australia.; University of Melbourne Department of Pediatrics, Parkville, Victoria, 3010, Australia., Morgan AT; Murdoch Children's Research Institute, Royal Children's Hospital, Flemington Rd, Parkville VIC, 3052, Australia.; University of Melbourne Department of Pediatrics, Parkville, Victoria, 3010, Australia., Kamien BA; Genetics Services of Western Australia, Perth, 6008, Western Australia., Patel C; Genetic Health Queensland, Royal Brisbane & Women's Hospital, Herston, QLD 4006, Australia., Tedder ML; Greenwood Genetic Center, Greenwood, SC 29646, United States., Merla G; Laboratory of Regulatory and Functional Genomics, Fondazione IRCCS Casa Sollievo della Sofferenza, 71013, San Giovanni Rotondo (Foggia), Italy.; Department of Molecular Medicine and Medical Biotechnology, University of Naples Federica II, 5 - 80131, Naples, Italy., Prontera P; Medical Genetics Unit, University of Perugia Hospital SM della Misericordia, Piazza dell'Università, 1, 06123, Perugia PG, Italy., Castori M; Division of Medical Genetics, Fondazione IRCCS Casa Sollievo della Sofferenza, 71013, San Giovanni Rotondo (Foggia), Italy., Muru K; Department of Clinical Genetics, United Laboratories, Tartu University Hospital, Riia 23b, 51010, Tartu, Estonia., Collins F; Discipline of Child and Adolescent Health and Genomic Medicine, Sydney Medical School, Sydney University, Sydney, Camperdown NSW, 2050, Australia.; Department of Clinical Genetics, Western Sydney Genetics Program, Children's Hospital at Westmead, Randwick NSW, 2031, Australia., Christodoulou J; Department of Clinical Genetics, Western Sydney Genetics Program, Children's Hospital at Westmead, Randwick NSW, 2031, Australia., Smith J; Sydney Children's Hospitals Network-Westmead, Randwick NSW, 2031, Australia.; University of Sydney, Camperdown NSW, 2006, Australia., Zeev BB; Sackler School of Medicine Tel Aviv University, Tel Aviv, 6997801, Israel., Murgia A; Laboratory of Molecular Genetics of Neurodevelopment, Department of Women's and Children's Health, University of Padua, Via Giustiniani 3, 35128, Padua, Italy., Leonardi E; Laboratory of Molecular Genetics of Neurodevelopment, Department of Women's and Children's Health, University of Padua, Via Giustiniani 3, 35128, Padua, Italy., Esber N; KAT6A Foundation, 3 Louise Dr., West Nyack, NY 10994, USA., Martinez-Monseny A; Genetics and Molecular Medicine Department, Rare Disease Pediatric Unit, Hospital Sant Joan de Déu, 2, 08950 Esplugues de Llobregat, Barcelona, Spain., Casas-Alba D; Genetics and Molecular Medicine Department, Rare Disease Pediatric Unit, Hospital Sant Joan de Déu, 2, 08950 Esplugues de Llobregat, Barcelona, Spain., Wallis M; Tasmanian Clinical Genetics Service, Tasmanian Health Service, Royal Hobart Hospital, Hobart, TAS 7001, Australia., Mannens M; Department of Human Genetics, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105, AZ, Amsterdam, The Netherlands., Levy MA; Molecular Genetics Laboratory, Molecular Diagnostics Division, London Health Sciences Centre, London, ON, N6A 5W9, Canada., Relator R; Molecular Genetics Laboratory, Molecular Diagnostics Division, London Health Sciences Centre, London, ON, N6A 5W9, Canada., Alders M; Department of Human Genetics, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105, AZ, Amsterdam, The Netherlands., Sadikovic B; Molecular Genetics Laboratory, Molecular Diagnostics Division, London Health Sciences Centre, London, ON, N6A 5W9, Canada.
Jazyk: angličtina
Zdroj: Epigenomics [Epigenomics] 2023 Mar; Vol. 15 (6), pp. 351-367. Date of Electronic Publication: 2023 May 30.
DOI: 10.2217/epi-2023-0079
Abstrakt: Accurate diagnosis for patients living with neurodevelopmental disorders is often met with numerous challenges, related to the ambiguity of findings and lack of specificity in genetic variants leading to pathology. Genome-wide DNA methylation analysis has been used to develop highly sensitive and specific 'episignatures' as biomarkers capable of differentiating and classifying complex neurodevelopmental disorders. In this study we describe distinct episignatures for KAT6A syndrome, caused by pathogenic variants in the lysine acetyltransferase A gene ( KAT6A ), and for the two neurodevelopmental disorders associated with lysine acetyl transferase B ( KAT6B ). We demonstrate the ability of our models to differentiate between highly overlapping episignatures, increasing the ability to effectively identify and diagnose these conditions.
Databáze: MEDLINE