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Detection of a DNA Methylation Signature for the Intellectual Developmental Disorder, X-Linked, Syndromic, Armfield Type
A growing number of genetic neurodevelopmental disorders are known to be associated with unique genomic DNA methylation patterns, called episignatures, which are detectable in peripheral blood. The intellectual developmental disorder, X-linked, syndromic, Armfield type (MRXSA) is caused by missense...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7865843/ https://www.ncbi.nlm.nih.gov/pubmed/33498634 http://dx.doi.org/10.3390/ijms22031111 |
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author | Haghshenas, Sadegheh Levy, Michael A. Kerkhof, Jennifer Aref-Eshghi, Erfan McConkey, Haley Balci, Tugce Siu, Victoria Mok Skinner, Cindy D. Stevenson, Roger E. Sadikovic, Bekim Schwartz, Charles |
author_facet | Haghshenas, Sadegheh Levy, Michael A. Kerkhof, Jennifer Aref-Eshghi, Erfan McConkey, Haley Balci, Tugce Siu, Victoria Mok Skinner, Cindy D. Stevenson, Roger E. Sadikovic, Bekim Schwartz, Charles |
author_sort | Haghshenas, Sadegheh |
collection | PubMed |
description | A growing number of genetic neurodevelopmental disorders are known to be associated with unique genomic DNA methylation patterns, called episignatures, which are detectable in peripheral blood. The intellectual developmental disorder, X-linked, syndromic, Armfield type (MRXSA) is caused by missense variants in FAM50A. Functional studies revealed the pathogenesis to be a spliceosomopathy that is characterized by atypical mRNA processing during development. In this study, we assessed the peripheral blood specimens in a cohort of individuals with MRXSA and detected a unique and highly specific DNA methylation episignature associated with this disorder. We used this episignature to construct a support vector machine model capable of sensitive and specific identification of individuals with pathogenic variants in FAM50A. This study contributes to the expanding number of genetic neurodevelopmental disorders with defined DNA methylation episignatures, provides an additional understanding of the associated molecular mechanisms, and further enhances our ability to diagnose patients with rare disorders. |
format | Online Article Text |
id | pubmed-7865843 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-78658432021-02-07 Detection of a DNA Methylation Signature for the Intellectual Developmental Disorder, X-Linked, Syndromic, Armfield Type Haghshenas, Sadegheh Levy, Michael A. Kerkhof, Jennifer Aref-Eshghi, Erfan McConkey, Haley Balci, Tugce Siu, Victoria Mok Skinner, Cindy D. Stevenson, Roger E. Sadikovic, Bekim Schwartz, Charles Int J Mol Sci Article A growing number of genetic neurodevelopmental disorders are known to be associated with unique genomic DNA methylation patterns, called episignatures, which are detectable in peripheral blood. The intellectual developmental disorder, X-linked, syndromic, Armfield type (MRXSA) is caused by missense variants in FAM50A. Functional studies revealed the pathogenesis to be a spliceosomopathy that is characterized by atypical mRNA processing during development. In this study, we assessed the peripheral blood specimens in a cohort of individuals with MRXSA and detected a unique and highly specific DNA methylation episignature associated with this disorder. We used this episignature to construct a support vector machine model capable of sensitive and specific identification of individuals with pathogenic variants in FAM50A. This study contributes to the expanding number of genetic neurodevelopmental disorders with defined DNA methylation episignatures, provides an additional understanding of the associated molecular mechanisms, and further enhances our ability to diagnose patients with rare disorders. MDPI 2021-01-23 /pmc/articles/PMC7865843/ /pubmed/33498634 http://dx.doi.org/10.3390/ijms22031111 Text en © 2021 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Haghshenas, Sadegheh Levy, Michael A. Kerkhof, Jennifer Aref-Eshghi, Erfan McConkey, Haley Balci, Tugce Siu, Victoria Mok Skinner, Cindy D. Stevenson, Roger E. Sadikovic, Bekim Schwartz, Charles Detection of a DNA Methylation Signature for the Intellectual Developmental Disorder, X-Linked, Syndromic, Armfield Type |
title | Detection of a DNA Methylation Signature for the Intellectual Developmental Disorder, X-Linked, Syndromic, Armfield Type |
title_full | Detection of a DNA Methylation Signature for the Intellectual Developmental Disorder, X-Linked, Syndromic, Armfield Type |
title_fullStr | Detection of a DNA Methylation Signature for the Intellectual Developmental Disorder, X-Linked, Syndromic, Armfield Type |
title_full_unstemmed | Detection of a DNA Methylation Signature for the Intellectual Developmental Disorder, X-Linked, Syndromic, Armfield Type |
title_short | Detection of a DNA Methylation Signature for the Intellectual Developmental Disorder, X-Linked, Syndromic, Armfield Type |
title_sort | detection of a dna methylation signature for the intellectual developmental disorder, x-linked, syndromic, armfield type |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7865843/ https://www.ncbi.nlm.nih.gov/pubmed/33498634 http://dx.doi.org/10.3390/ijms22031111 |
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