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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...

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Autores principales: 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
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
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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.
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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
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