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Genomic Aberrations Associated with the Pathophysiological Mechanisms of Neurodevelopmental Disorders
Genomic studies are increasingly revealing that neurodevelopmental disorders are caused by underlying genomic alterations. Chromosomal microarray testing has been used to reliably detect minute changes in genomic copy numbers. The genes located in the aberrated regions identified in patients with ne...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8470284/ https://www.ncbi.nlm.nih.gov/pubmed/34571966 http://dx.doi.org/10.3390/cells10092317 |
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author | Yamamoto, Toshiyuki |
author_facet | Yamamoto, Toshiyuki |
author_sort | Yamamoto, Toshiyuki |
collection | PubMed |
description | Genomic studies are increasingly revealing that neurodevelopmental disorders are caused by underlying genomic alterations. Chromosomal microarray testing has been used to reliably detect minute changes in genomic copy numbers. The genes located in the aberrated regions identified in patients with neurodevelopmental disorders may be associated with the phenotypic features. In such cases, haploinsufficiency is considered to be the mechanism, when the deletion of a gene is related to neurodevelopmental delay. The loss-of-function mutation in such genes may be evaluated using next-generation sequencing. On the other hand, the patients with increased copy numbers of the genes may exhibit different clinical symptoms compared to those with loss-of-function mutation in the genes. In such cases, the additional copies of the genes are considered to have a dominant negative effect, inducing cell stress. In other cases, not the copy number changes, but mutations of the genes are responsible for causing the clinical symptoms. This can be explained by the dominant negative effects of the gene mutations. Currently, the diagnostic yield of genomic alterations using comprehensive analysis is less than 50%, indicating the existence of more subtle alterations or genomic changes in the untranslated regions. Copy-neutral inversions and insertions may be related. Hence, better analytical algorithms specialized for the detection of such alterations are required for higher diagnostic yields. |
format | Online Article Text |
id | pubmed-8470284 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-84702842021-09-27 Genomic Aberrations Associated with the Pathophysiological Mechanisms of Neurodevelopmental Disorders Yamamoto, Toshiyuki Cells Review Genomic studies are increasingly revealing that neurodevelopmental disorders are caused by underlying genomic alterations. Chromosomal microarray testing has been used to reliably detect minute changes in genomic copy numbers. The genes located in the aberrated regions identified in patients with neurodevelopmental disorders may be associated with the phenotypic features. In such cases, haploinsufficiency is considered to be the mechanism, when the deletion of a gene is related to neurodevelopmental delay. The loss-of-function mutation in such genes may be evaluated using next-generation sequencing. On the other hand, the patients with increased copy numbers of the genes may exhibit different clinical symptoms compared to those with loss-of-function mutation in the genes. In such cases, the additional copies of the genes are considered to have a dominant negative effect, inducing cell stress. In other cases, not the copy number changes, but mutations of the genes are responsible for causing the clinical symptoms. This can be explained by the dominant negative effects of the gene mutations. Currently, the diagnostic yield of genomic alterations using comprehensive analysis is less than 50%, indicating the existence of more subtle alterations or genomic changes in the untranslated regions. Copy-neutral inversions and insertions may be related. Hence, better analytical algorithms specialized for the detection of such alterations are required for higher diagnostic yields. MDPI 2021-09-04 /pmc/articles/PMC8470284/ /pubmed/34571966 http://dx.doi.org/10.3390/cells10092317 Text en © 2021 by the author. 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 | Review Yamamoto, Toshiyuki Genomic Aberrations Associated with the Pathophysiological Mechanisms of Neurodevelopmental Disorders |
title | Genomic Aberrations Associated with the Pathophysiological Mechanisms of Neurodevelopmental Disorders |
title_full | Genomic Aberrations Associated with the Pathophysiological Mechanisms of Neurodevelopmental Disorders |
title_fullStr | Genomic Aberrations Associated with the Pathophysiological Mechanisms of Neurodevelopmental Disorders |
title_full_unstemmed | Genomic Aberrations Associated with the Pathophysiological Mechanisms of Neurodevelopmental Disorders |
title_short | Genomic Aberrations Associated with the Pathophysiological Mechanisms of Neurodevelopmental Disorders |
title_sort | genomic aberrations associated with the pathophysiological mechanisms of neurodevelopmental disorders |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8470284/ https://www.ncbi.nlm.nih.gov/pubmed/34571966 http://dx.doi.org/10.3390/cells10092317 |
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