Cargando…
Identification of a DNA Methylation Episignature in the 22q11.2 Deletion Syndrome
The 22q11.2 deletion syndrome (22q11.2DS) is the most common genomic disorder in humans and is the result of a recurrent 1.5 to 2.5 Mb deletion, encompassing approximately 20–40 genes, respectively. The clinical presentation of the typical deletion includes: Velocardiofacial, Di George, Opitz G/BBB...
Autores principales: | , , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8395258/ https://www.ncbi.nlm.nih.gov/pubmed/34445317 http://dx.doi.org/10.3390/ijms22168611 |
_version_ | 1783744132465819648 |
---|---|
author | Rooney, Kathleen Levy, Michael A. Haghshenas, Sadegheh Kerkhof, Jennifer Rogaia, Daniela Tedesco, Maria Giovanna Imperatore, Valentina Mencarelli, Amedea Squeo, Gabriella Maria Di Venere, Eleonora Di Cara, Giuseppe Verrotti, Alberto Merla, Giuseppe Tedder, Matthew L. DuPont, Barbara R. Sadikovic, Bekim Prontera, Paolo |
author_facet | Rooney, Kathleen Levy, Michael A. Haghshenas, Sadegheh Kerkhof, Jennifer Rogaia, Daniela Tedesco, Maria Giovanna Imperatore, Valentina Mencarelli, Amedea Squeo, Gabriella Maria Di Venere, Eleonora Di Cara, Giuseppe Verrotti, Alberto Merla, Giuseppe Tedder, Matthew L. DuPont, Barbara R. Sadikovic, Bekim Prontera, Paolo |
author_sort | Rooney, Kathleen |
collection | PubMed |
description | The 22q11.2 deletion syndrome (22q11.2DS) is the most common genomic disorder in humans and is the result of a recurrent 1.5 to 2.5 Mb deletion, encompassing approximately 20–40 genes, respectively. The clinical presentation of the typical deletion includes: Velocardiofacial, Di George, Opitz G/BBB and Conotruncalanomaly face syndromes. Atypical deletions (proximal, distal or nested) are rare and characterized mainly by normal phenotype or mild intellectual disability and variable clinical features. The pathogenetic mechanisms underlying this disorder are not completely understood. Because the 22q11.2 region harbours genes coding for transcriptional factors and chromatin remodelers, in this study, we performed analysis of genome-wide DNA methylation of peripheral blood from 49 patients with 22q11.2DS using the Illumina Infinium Methylation EPIC bead chip arrays. This cohort comprises 43 typical, 2 proximal and 4 distal deletions. We demonstrated the evidence of a unique and highly specific episignature in all typical and proximal 22q11.2DS. The sensitivity and specificity of this signature was further confirmed by comparing it to over 1500 patients with other neurodevelopmental disorders with known episignatures. Mapping the 22q11.2DS DNA methylation episignature provides both novel insights into the molecular pathogenesis of this disorder and an effective tool in the molecular diagnosis of 22q11.2DS. |
format | Online Article Text |
id | pubmed-8395258 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-83952582021-08-28 Identification of a DNA Methylation Episignature in the 22q11.2 Deletion Syndrome Rooney, Kathleen Levy, Michael A. Haghshenas, Sadegheh Kerkhof, Jennifer Rogaia, Daniela Tedesco, Maria Giovanna Imperatore, Valentina Mencarelli, Amedea Squeo, Gabriella Maria Di Venere, Eleonora Di Cara, Giuseppe Verrotti, Alberto Merla, Giuseppe Tedder, Matthew L. DuPont, Barbara R. Sadikovic, Bekim Prontera, Paolo Int J Mol Sci Article The 22q11.2 deletion syndrome (22q11.2DS) is the most common genomic disorder in humans and is the result of a recurrent 1.5 to 2.5 Mb deletion, encompassing approximately 20–40 genes, respectively. The clinical presentation of the typical deletion includes: Velocardiofacial, Di George, Opitz G/BBB and Conotruncalanomaly face syndromes. Atypical deletions (proximal, distal or nested) are rare and characterized mainly by normal phenotype or mild intellectual disability and variable clinical features. The pathogenetic mechanisms underlying this disorder are not completely understood. Because the 22q11.2 region harbours genes coding for transcriptional factors and chromatin remodelers, in this study, we performed analysis of genome-wide DNA methylation of peripheral blood from 49 patients with 22q11.2DS using the Illumina Infinium Methylation EPIC bead chip arrays. This cohort comprises 43 typical, 2 proximal and 4 distal deletions. We demonstrated the evidence of a unique and highly specific episignature in all typical and proximal 22q11.2DS. The sensitivity and specificity of this signature was further confirmed by comparing it to over 1500 patients with other neurodevelopmental disorders with known episignatures. Mapping the 22q11.2DS DNA methylation episignature provides both novel insights into the molecular pathogenesis of this disorder and an effective tool in the molecular diagnosis of 22q11.2DS. MDPI 2021-08-10 /pmc/articles/PMC8395258/ /pubmed/34445317 http://dx.doi.org/10.3390/ijms22168611 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Rooney, Kathleen Levy, Michael A. Haghshenas, Sadegheh Kerkhof, Jennifer Rogaia, Daniela Tedesco, Maria Giovanna Imperatore, Valentina Mencarelli, Amedea Squeo, Gabriella Maria Di Venere, Eleonora Di Cara, Giuseppe Verrotti, Alberto Merla, Giuseppe Tedder, Matthew L. DuPont, Barbara R. Sadikovic, Bekim Prontera, Paolo Identification of a DNA Methylation Episignature in the 22q11.2 Deletion Syndrome |
title | Identification of a DNA Methylation Episignature in the 22q11.2 Deletion Syndrome |
title_full | Identification of a DNA Methylation Episignature in the 22q11.2 Deletion Syndrome |
title_fullStr | Identification of a DNA Methylation Episignature in the 22q11.2 Deletion Syndrome |
title_full_unstemmed | Identification of a DNA Methylation Episignature in the 22q11.2 Deletion Syndrome |
title_short | Identification of a DNA Methylation Episignature in the 22q11.2 Deletion Syndrome |
title_sort | identification of a dna methylation episignature in the 22q11.2 deletion syndrome |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8395258/ https://www.ncbi.nlm.nih.gov/pubmed/34445317 http://dx.doi.org/10.3390/ijms22168611 |
work_keys_str_mv | AT rooneykathleen identificationofadnamethylationepisignatureinthe22q112deletionsyndrome AT levymichaela identificationofadnamethylationepisignatureinthe22q112deletionsyndrome AT haghshenassadegheh identificationofadnamethylationepisignatureinthe22q112deletionsyndrome AT kerkhofjennifer identificationofadnamethylationepisignatureinthe22q112deletionsyndrome AT rogaiadaniela identificationofadnamethylationepisignatureinthe22q112deletionsyndrome AT tedescomariagiovanna identificationofadnamethylationepisignatureinthe22q112deletionsyndrome AT imperatorevalentina identificationofadnamethylationepisignatureinthe22q112deletionsyndrome AT mencarelliamedea identificationofadnamethylationepisignatureinthe22q112deletionsyndrome AT squeogabriellamaria identificationofadnamethylationepisignatureinthe22q112deletionsyndrome AT divenereeleonora identificationofadnamethylationepisignatureinthe22q112deletionsyndrome AT dicaragiuseppe identificationofadnamethylationepisignatureinthe22q112deletionsyndrome AT verrottialberto identificationofadnamethylationepisignatureinthe22q112deletionsyndrome AT merlagiuseppe identificationofadnamethylationepisignatureinthe22q112deletionsyndrome AT teddermatthewl identificationofadnamethylationepisignatureinthe22q112deletionsyndrome AT dupontbarbarar identificationofadnamethylationepisignatureinthe22q112deletionsyndrome AT sadikovicbekim identificationofadnamethylationepisignatureinthe22q112deletionsyndrome AT pronterapaolo identificationofadnamethylationepisignatureinthe22q112deletionsyndrome |