DNA Methylation Episignatures in Neurodevelopmental Disorders Associated with Large Structural Copy Number Variants: Clinical Implications
Large structural chromosomal deletions and duplications, referred to as copy number variants (CNVs), play a role in the pathogenesis of neurodevelopmental disorders (NDDs) through effects on gene dosage. This review focuses on our current understanding of genomic disorders that arise from large stru...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-07-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/14/7862 |
| _version_ | 1797433447970504704 |
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| author | Kathleen Rooney Bekim Sadikovic |
| author_facet | Kathleen Rooney Bekim Sadikovic |
| author_sort | Kathleen Rooney |
| collection | DOAJ |
| description | Large structural chromosomal deletions and duplications, referred to as copy number variants (CNVs), play a role in the pathogenesis of neurodevelopmental disorders (NDDs) through effects on gene dosage. This review focuses on our current understanding of genomic disorders that arise from large structural chromosome rearrangements in patients with NDDs, as well as difficulties in overlap of clinical presentation and molecular diagnosis. We discuss the implications of epigenetics, specifically DNA methylation (DNAm), in NDDs and genomic disorders, and consider the implications and clinical impact of copy number and genomic DNAm testing in patients with suspected genetic NDDs. We summarize evidence of global methylation episignatures in CNV-associated disorders that can be used in the diagnostic pathway and may provide insights into the molecular pathogenesis of genomic disorders. Finally, we discuss the potential for combining CNV and DNAm assessment into a single diagnostic assay. |
| first_indexed | 2024-03-09T10:17:11Z |
| format | Article |
| id | doaj.art-4594a129efb7485ebc0bb1b1bd15bfd0 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T10:17:11Z |
| publishDate | 2022-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-4594a129efb7485ebc0bb1b1bd15bfd02023-12-01T22:15:55ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-07-012314786210.3390/ijms23147862DNA Methylation Episignatures in Neurodevelopmental Disorders Associated with Large Structural Copy Number Variants: Clinical ImplicationsKathleen Rooney0Bekim Sadikovic1Department of Pathology and Laboratory Medicine, Western University, London, ON N6A 3K7, CanadaDepartment of Pathology and Laboratory Medicine, Western University, London, ON N6A 3K7, CanadaLarge structural chromosomal deletions and duplications, referred to as copy number variants (CNVs), play a role in the pathogenesis of neurodevelopmental disorders (NDDs) through effects on gene dosage. This review focuses on our current understanding of genomic disorders that arise from large structural chromosome rearrangements in patients with NDDs, as well as difficulties in overlap of clinical presentation and molecular diagnosis. We discuss the implications of epigenetics, specifically DNA methylation (DNAm), in NDDs and genomic disorders, and consider the implications and clinical impact of copy number and genomic DNAm testing in patients with suspected genetic NDDs. We summarize evidence of global methylation episignatures in CNV-associated disorders that can be used in the diagnostic pathway and may provide insights into the molecular pathogenesis of genomic disorders. Finally, we discuss the potential for combining CNV and DNAm assessment into a single diagnostic assay.https://www.mdpi.com/1422-0067/23/14/7862DNA methylationepisignatureepigeneticscopy number variantneurodevelopmental disordergenomic disorder |
| spellingShingle | Kathleen Rooney Bekim Sadikovic DNA Methylation Episignatures in Neurodevelopmental Disorders Associated with Large Structural Copy Number Variants: Clinical Implications International Journal of Molecular Sciences DNA methylation episignature epigenetics copy number variant neurodevelopmental disorder genomic disorder |
| title | DNA Methylation Episignatures in Neurodevelopmental Disorders Associated with Large Structural Copy Number Variants: Clinical Implications |
| title_full | DNA Methylation Episignatures in Neurodevelopmental Disorders Associated with Large Structural Copy Number Variants: Clinical Implications |
| title_fullStr | DNA Methylation Episignatures in Neurodevelopmental Disorders Associated with Large Structural Copy Number Variants: Clinical Implications |
| title_full_unstemmed | DNA Methylation Episignatures in Neurodevelopmental Disorders Associated with Large Structural Copy Number Variants: Clinical Implications |
| title_short | DNA Methylation Episignatures in Neurodevelopmental Disorders Associated with Large Structural Copy Number Variants: Clinical Implications |
| title_sort | dna methylation episignatures in neurodevelopmental disorders associated with large structural copy number variants clinical implications |
| topic | DNA methylation episignature epigenetics copy number variant neurodevelopmental disorder genomic disorder |
| url | https://www.mdpi.com/1422-0067/23/14/7862 |
| work_keys_str_mv | AT kathleenrooney dnamethylationepisignaturesinneurodevelopmentaldisordersassociatedwithlargestructuralcopynumbervariantsclinicalimplications AT bekimsadikovic dnamethylationepisignaturesinneurodevelopmentaldisordersassociatedwithlargestructuralcopynumbervariantsclinicalimplications |