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Distinct Roles of Histone Lysine Demethylases and Methyltransferases in Developmental Eye Disease

Histone lysine methyltransferase and demethylase enzymes play a central role in chromatin organization and gene expression through the dynamic regulation of histone lysine methylation. Consistent with this, genes encoding for histone lysine methyltransferases (KMTs) and demethylases (KDMs) are invol...

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Autores principales: Reis, Linda M., Atilla, Huban, Kannu, Peter, Schneider, Adele, Thompson, Samuel, Bardakjian, Tanya, Semina, Elena V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9859058/
https://www.ncbi.nlm.nih.gov/pubmed/36672956
http://dx.doi.org/10.3390/genes14010216
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author Reis, Linda M.
Atilla, Huban
Kannu, Peter
Schneider, Adele
Thompson, Samuel
Bardakjian, Tanya
Semina, Elena V.
author_facet Reis, Linda M.
Atilla, Huban
Kannu, Peter
Schneider, Adele
Thompson, Samuel
Bardakjian, Tanya
Semina, Elena V.
author_sort Reis, Linda M.
collection PubMed
description Histone lysine methyltransferase and demethylase enzymes play a central role in chromatin organization and gene expression through the dynamic regulation of histone lysine methylation. Consistent with this, genes encoding for histone lysine methyltransferases (KMTs) and demethylases (KDMs) are involved in complex human syndromes, termed congenital regulopathies. In this report, we present several lines of evidence for the involvement of these genes in developmental ocular phenotypes, suggesting that individuals with structural eye defects, especially when accompanied by craniofacial, neurodevelopmental and growth abnormalities, should be examined for possible variants in these genes. We identified nine heterozygous damaging genetic variants in KMT2D (5) and four other histone lysine methyltransferases/demethylases (KMT2C, SETD1A/KMT2F, KDM6A and KDM5C) in unrelated families affected with developmental eye disease, such as Peters anomaly, sclerocornea, Axenfeld-Rieger spectrum, microphthalmia and coloboma. Two families were clinically diagnosed with Axenfeld-Rieger syndrome and two were diagnosed with Peters plus-like syndrome; others received no specific diagnosis prior to genetic testing. All nine alleles were novel and five of them occurred de novo; five variants resulted in premature truncation, three were missense changes and one was an in-frame deletion/insertion; and seven variants were categorized as pathogenic or likely pathogenic and two were variants of uncertain significance. This study expands the phenotypic spectra associated with KMT and KDM factors and highlights the importance of genetic testing for correct clinical diagnosis.
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spelling pubmed-98590582023-01-21 Distinct Roles of Histone Lysine Demethylases and Methyltransferases in Developmental Eye Disease Reis, Linda M. Atilla, Huban Kannu, Peter Schneider, Adele Thompson, Samuel Bardakjian, Tanya Semina, Elena V. Genes (Basel) Brief Report Histone lysine methyltransferase and demethylase enzymes play a central role in chromatin organization and gene expression through the dynamic regulation of histone lysine methylation. Consistent with this, genes encoding for histone lysine methyltransferases (KMTs) and demethylases (KDMs) are involved in complex human syndromes, termed congenital regulopathies. In this report, we present several lines of evidence for the involvement of these genes in developmental ocular phenotypes, suggesting that individuals with structural eye defects, especially when accompanied by craniofacial, neurodevelopmental and growth abnormalities, should be examined for possible variants in these genes. We identified nine heterozygous damaging genetic variants in KMT2D (5) and four other histone lysine methyltransferases/demethylases (KMT2C, SETD1A/KMT2F, KDM6A and KDM5C) in unrelated families affected with developmental eye disease, such as Peters anomaly, sclerocornea, Axenfeld-Rieger spectrum, microphthalmia and coloboma. Two families were clinically diagnosed with Axenfeld-Rieger syndrome and two were diagnosed with Peters plus-like syndrome; others received no specific diagnosis prior to genetic testing. All nine alleles were novel and five of them occurred de novo; five variants resulted in premature truncation, three were missense changes and one was an in-frame deletion/insertion; and seven variants were categorized as pathogenic or likely pathogenic and two were variants of uncertain significance. This study expands the phenotypic spectra associated with KMT and KDM factors and highlights the importance of genetic testing for correct clinical diagnosis. MDPI 2023-01-14 /pmc/articles/PMC9859058/ /pubmed/36672956 http://dx.doi.org/10.3390/genes14010216 Text en © 2023 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 Brief Report
Reis, Linda M.
Atilla, Huban
Kannu, Peter
Schneider, Adele
Thompson, Samuel
Bardakjian, Tanya
Semina, Elena V.
Distinct Roles of Histone Lysine Demethylases and Methyltransferases in Developmental Eye Disease
title Distinct Roles of Histone Lysine Demethylases and Methyltransferases in Developmental Eye Disease
title_full Distinct Roles of Histone Lysine Demethylases and Methyltransferases in Developmental Eye Disease
title_fullStr Distinct Roles of Histone Lysine Demethylases and Methyltransferases in Developmental Eye Disease
title_full_unstemmed Distinct Roles of Histone Lysine Demethylases and Methyltransferases in Developmental Eye Disease
title_short Distinct Roles of Histone Lysine Demethylases and Methyltransferases in Developmental Eye Disease
title_sort distinct roles of histone lysine demethylases and methyltransferases in developmental eye disease
topic Brief Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9859058/
https://www.ncbi.nlm.nih.gov/pubmed/36672956
http://dx.doi.org/10.3390/genes14010216
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