New insights into DNA methylation signatures: SMARCA2 variants in Nicolaides-Baraitser syndrome View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-07-09

AUTHORS

Eric Chater-Diehl, Resham Ejaz, Cheryl Cytrynbaum, Michelle T. Siu, Andrei Turinsky, Sanaa Choufani, Sarah J. Goodman, Omar Abdul-Rahman, Melanie Bedford, Naghmeh Dorrani, Kendra Engleman, Josue Flores-Daboub, David Genevieve, Roberto Mendoza-Londono, Wendy Meschino, Laurence Perrin, Nicole Safina, Sharron Townshend, Stephen W. Scherer, Evdokia Anagnostou, Amelie Piton, Matthew Deardorff, Michael Brudno, David Chitayat, Rosanna Weksberg

ABSTRACT

BACKGROUND: Nicolaides-Baraitser syndrome (NCBRS) is a neurodevelopmental disorder caused by pathogenic sequence variants in SMARCA2 which encodes the catalytic component of the chromatin remodeling BAF complex. Pathogenic variants in genes that encode epigenetic regulators have been associated with genome-wide changes in DNA methylation (DNAm) in affected individuals termed DNAm signatures. METHODS: Genome-wide DNAm was assessed in whole-blood samples from the individuals with pathogenic SMARCA2 variants and NCBRS diagnosis (n = 8) compared to neurotypical controls (n = 23) using the Illumina MethylationEPIC array. Differential methylated CpGs between groups (DNAm signature) were identified and used to generate a model enabling classification variants of uncertain significance (VUS; n = 9) in SMARCA2 as "pathogenic" or "benign". A validation cohort of NCBRS cases (n = 8) and controls (n = 96) demonstrated 100% model sensitivity and specificity. RESULTS: We identified a DNAm signature of 429 differentially methylated CpG sites in individuals with NCBRS. The genes to which these CpG sites map are involved in cell differentiation, calcium signaling, and neuronal function consistent with NCBRS pathophysiology. DNAm model classifications of VUS were concordant with the clinical phenotype; those within the SMARCA2 ATPase/helicase domain classified as "pathogenic". A patient with a mild neurodevelopmental NCBRS phenotype and a VUS distal to the ATPase/helicase domain did not score as pathogenic, clustering away from cases and controls. She demonstrated an intermediate DNAm profile consisting of one subset of signature CpGs with methylation levels characteristic of controls and another characteristic of NCBRS cases; each mapped to genes with ontologies consistent with the patient's unique clinical presentation. CONCLUSIONS: Here we find that a DNAm signature of SMARCA2 pathogenic variants in NCBRS maps to CpGs relevant to disorder pathophysiology, classifies VUS, and is sensitive to the position of the variant in SMARCA2. The patient with an intermediate model score demonstrating a unique genotype-epigenotype-phenotype correlation underscores the potential utility of this signature as a functionally relevant VUS classification system scalable beyond binary "benign" versus "pathogenic" scoring. This is a novel feature of DNAm signatures that could enable phenotypic predictions from genotype data. Our findings also demonstrate that DNAm signatures can be domain-specific, highlighting the precision with which they can reflect genotypic variation. More... »

PAGES

105

References to SciGraph publications

  • 2018-11-20. BAFopathies’ DNA methylation epi-signatures demonstrate diagnostic utility and functional continuum of Coffin–Siris and Nicolaides–Baraitser syndromes in NATURE COMMUNICATIONS
  • 2016-09-05. Identification of a methylation profile for DNMT1-associated autosomal dominant cerebellar ataxia, deafness, and narcolepsy in CLINICAL EPIGENETICS
  • 2010-01-27. Chromatin remodelling during development in NATURE
  • 2015-07-10. An evaluation of statistical methods for DNA methylation microarray data analysis in BMC BIOINFORMATICS
  • 2018-05-29. An optimized library for reference-based deconvolution of whole-blood biospecimens assayed using the Illumina HumanMethylationEPIC BeadArray in GENOME BIOLOGY
  • 2017-11-07. Patients with a Kabuki syndrome phenotype demonstrate DNA methylation abnormalities in EUROPEAN JOURNAL OF HUMAN GENETICS
  • 2015-05-13. Assessment of the predictive accuracy of five in silico prediction tools, alone or in combination, and two metaservers to classify long QT syndrome gene mutations in BMC MEDICAL GENETICS
  • 2015-02-28. Exome sequencing unravels unexpected differential diagnoses in individuals with the tentative diagnosis of Coffin–Siris and Nicolaides–Baraitser syndromes in HUMAN GENETICS
  • 2012-03-18. Mutations in SWI/SNF chromatin remodeling complex gene ARID1B cause Coffin-Siris syndrome in NATURE GENETICS
  • 2013-01-28. Multilocus loss of DNA methylation in individuals with mutations in the histone H3 Lysine 4 Demethylase KDM5C in BMC MEDICAL GENOMICS
  • 2015-12-22. NSD1 mutations generate a genome-wide DNA methylation signature in NATURE COMMUNICATIONS
  • 2010-08-15. Exome sequencing identifies MLL2 mutations as a cause of Kabuki syndrome in NATURE GENETICS
  • 2010-05-02. GREAT improves functional interpretation of cis-regulatory regions in NATURE BIOTECHNOLOGY
  • 2013-10-21. DNA methylation age of human tissues and cell types in GENOME BIOLOGY
  • 2019-07-16. Functional DNA methylation signatures for autism spectrum disorder genomic risk loci: 16p11.2 deletions and CHD8 variants in CLINICAL EPIGENETICS
  • 2012-03-18. Mutations affecting components of the SWI/SNF complex cause Coffin-Siris syndrome in NATURE GENETICS
  • 2012-02-26. Heterozygous missense mutations in SMARCA2 cause Nicolaides-Baraitser syndrome in NATURE GENETICS
  • Journal

    TITLE

    BMC Medical Genomics

    ISSUE

    1

    VOLUME

    12

    Author Affiliations

  • Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario M5G 1X8 Canada
  • Division of Genetics, Department of Pediatrics, McMaster University, Hamilton, Ontario L8S 4L8 Canada
  • Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A1 Canada
  • Centre for Computational Medicine, The Hospital for Sick Children, Toronto, Ontario M5G 1X8 Canada
  • Department of Genetic Medicine, Munroe-Meyer Institute, University of Nebraska Medical Center, Omaha, NE USA
  • Department of Paediatrics, University of Toronto, Toronto, Ontario M5S 3H7 Canada
  • Department of Pediatrics, UCLA, Los Angeles, CA 90095 USA
  • Division of Clinical Genetics, Children’s Mercy Hospital, Kansas City, MO 66111 USA
  • Division of Pediatric Clinical Genetics, University of Utah School of Medicine, Salt Lake City, UT 84132 USA
  • Service de génétique clinique, Département de génétique médicale, maladies rares, médecine personnalisée, Unité INSERM U1183, Université Montpellier, CHU Montpellier, 34000 Montpellier, France
  • Department of Pediatrics, University of Toronto, Toronto, Ontario M5S 1A1 Canada
  • Genetics Program, North York General Hospital, Toronto, Ontario M2K 1E1 Canada
  • AP-HP, Department of Genetics, Hôpital Robert Debré, 75019 Paris, France
  • Department of Pediatrics, Children’s Mercy Hospital, Kansas City, MO 64108 USA
  • Department of Health, Government of Western Australia, Genetic Services of Western Australia, Perth, WA Australia
  • McLaughlin Centre, University of Toronto, Toronto, Ontario M5S 1A1 Canada
  • Institute of Medical Science, University of Toronto, Toronto, Ontario M5S 1A1 Canada
  • Laboratoire de Diagnostic Génétique, Nouvel Hôpital Civil, Hôpitaux Universitaires de Strasbourg, 67000 Strasbourg, France
  • The Department of Pediatrics, The Perelman School of Medicine, The University of Pennsylvania, Philadelphia, PA 19104 USA
  • Department of Computer Science, University of Toronto, Toronto, Ontario M5S 1A1 Canada
  • Prenatal Diagnosis and Medical Genetics Program, Mount Sinai Hospital, Toronto, Ontario M5G 1X5 Canada
  • Institute of Medical Sciences, University of Toronto, Toronto, Ontario M5S 1A8 Canada
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1186/s12920-019-0555-y

    DOI

    http://dx.doi.org/10.1186/s12920-019-0555-y

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1117870766

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/31288860


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