ArticleAmerican journal of human genetics2019
Diagnostic Utility of Genome-wide DNA Methylation Testing in Genetically Unsolved Individuals with Suspected Hereditary Conditions.
Article in American journal of human genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 117 papers.
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Who cites it
117 citing papers in PubMed, 200 citations in OpenAlex.
- Clinical Epigenomics in Rare Diseases: Interpreting DNA Methylation Episignatures.Molecular genetics & genomic medicine · 2026Review
- An episignature informed systematic analysis to ascertain the clinical significance and consequences of CHD8 missense variants.European journal of human genetics : EJHG · 2026Article
- Biallelic inactivating variants in the chromatin remodeler DMAP1 cause a syndromic neurodevelopmental disorder.The Journal of clinical investigation · 2026Article
- Discovery of a DNA methylation episignature for Weiss-Kruszka syndrome.Human genetics · 2026Article
- De novo EHMT2 variants cause an autosomal dominant EHMT2-related Kleefstra syndrome via loss of G9a methyltransferase activity.Nature communications · 2026Article
- Ensilication preserves high-molecular weight native DNA for clinical long-read sequencing.Genome biology · 2026Article
- DNA methylation signature and clinical delineation of PACS1-related disorder in 24 unreported individuals.European journal of human genetics : EJHG · 2026Article
- Chromatinopathies: clinically overlapping disorders, revealing novel variants and their DNA methylation signatures.Clinical epigenetics · 2026Article
- DNA Methylation Episignature as a Novel Diagnostic Tool for Diamond-Blackfan Anemia Syndrome.American journal of hematology · 2026Article
- Genome-wide methylation detection and episignature analysis using PacBio long-read sequencing.Genome medicine · 2026Article
- DNA methylation analysis of NOTCH1 variants reveals the first episignature for non-syndromic congenital heart defects.Genome medicine · 2026Article
- A role forFrontiers in genetics · 2026Article
- Identification of an episignature for the MEF2C-associated syndrome.European journal of human genetics : EJHG · 2026Article
- DNA methylation episignature for Smith-Magenis and Potocki-Lupski syndromes: a mirror perspective.European journal of human genetics : EJHG · 2026Article
- Episignature leads to diagnosis and reclassification of DYRK1A variant in a child with syndromic neurodevelopmental disorder: a case report.Frontiers in genetics · 2026Article
- Analysis Methods for Diagnosing Rare Neurodevelopmental Diseases with Episignatures: A Systematic Review of the Literature.Biomedicines · 2025Review
- Investigation of methylation profiles in Silver-Russell syndrome to explore episignatures.Clinical epigenetics · 2025Article
- ARID2-related disorder: further delineation of the clinical phenotype of 27 novel individuals and description of an epigenetic signature.European journal of human genetics : EJHG · 2025Article
- DNA Methylation at a Single Locus of Human Genome Accurately Recapitulates Episignature of CREBBP-Related Rubinstein-Taybi Syndrome.International journal of molecular sciences · 2025Article
- Biallelic loss-of-function variants in ZNF142 are associated with a robust DNA methylation signature affecting a limited number of genomic loci.European journal of human genetics : EJHG · 2025Article
57 more citing papers are in PubMed but not listed here.
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Authors and funding
27 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Conventional genetic testing of individuals with neurodevelopmental presentations and congenital anomalies (ND/CAs), i.e., the analysis of sequence and copy number variants, leaves a substantial proportion of them unexplained. Some of these cases have been shown to result from DNA methylation defects at a single locus (epi-variants), while others can exhibit syndrome-specific DNA methylation changes across multiple loci (epi-signatures). Here, we investigate the clinical diagnostic utility of genome-wide DNA methylation analysis of peripheral blood in unresolved ND/CAs. We generate a computational model enabling concurrent detection of 14 syndromes using DNA methylation data with full accuracy. We demonstrate the ability of this model in resolving 67 individuals with uncertain clinical diagnoses, some of whom had variants of unknown clinical significance (VUS) in the related genes. We show that the provisional diagnoses can be ruled out in many of the case subjects, some of whom are shown by our model to have other diseases initially not considered. By applying this model to a cohort of 965 ND/CA-affected subjects without a previous diagnostic assumption and a separate assessment of rare epi-variants in this cohort, we identify 15 case subjects with syndromic Mendelian disorders, 12 case subjects with imprinting and trinucleotide repeat expansion disorders, as well as 106 case subjects with rare epi-variants, a portion of which involved genes clinically or functionally linked to the subjects' phenotypes. This study demonstrates that genomic DNA methylation analysis can facilitate the molecular diagnosis of unresolved clinical cases and highlights the potential value of epigenomic testing in the routine clinical assessment of ND/CAs.
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