Diagnostic Utility of Genome-wide DNA Methylation Testing in Genetically Unsolved Individuals with Suspected Hereditary Conditions

• Published in: American journal of human genetics Vol. 104; no. 4; pp. 685 - 700
• Main Authors: Aref-Eshghi, Erfan, Bend, Eric G., Colaiacovo, Samantha, Caudle, Michelle, Chakrabarti, Rana, Napier, Melanie, Brick, Lauren, Brady, Lauren, Carere, Deanna Alexis, Levy, Michael A., Kerkhof, Jennifer, Stuart, Alan, Saleh, Maha, Beaudet, Arthur L., Li, Chumei, Kozenko, Maryia, Karp, Natalya, Prasad, Chitra, Siu, Victoria Mok, Tarnopolsky, Mark A., Ainsworth, Peter J., Lin, Hanxin, Rodenhiser, David I., Krantz, Ian D., Deardorff, Matthew A., Schwartz, Charles E., Sadikovic, Bekim
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 04.04.2019; Elsevier
• Subjects: clinical epigenomic testing; Cohort Studies; Computer Simulation; Congenital Abnormalities - diagnosis; Congenital Abnormalities - genetics; congenital anomaly; DNA Copy Number Variations; DNA Methylation; epi-signature; epi-variant; Epigenomics; Gene Dosage; Genetic Diseases, Inborn - diagnosis; Genetic Diseases, Inborn - genetics; Genetic Variation; Genome-Wide Association Study; Genomic Imprinting; Humans; imprinting; multiclass prediction; neurodevelopmental syndrome; nucleotide expansion repeat; Phenotype; Sequence Analysis, DNA; Syndrome; Trinucleotide Repeat Expansion; unresolved case; variant of unknown significance; unresolved case; epi-signature; imprinting; neurodevelopmental syndrome; nucleotide expansion repeat; variant of unknown significance; DNA methylation; multiclass prediction; epi-variant; clinical epigenomic testing; congenital anomaly

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 defect...