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Expanding the Spectrum of KDM5C Neurodevelopmental Disorder: A Novel De Novo Stop Variant in a Young Woman and Emerging Genotype–Phenotype Correlations

As a consequence of the implementation of NGS technologies, the diagnostic yield of neurodevelopmental disorders has dramatically increased during the past two decades. Among neurodevelopmental genes, transcription-related genes and chromatin remodeling genes are the most represented category of dis...

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Autores principales: Lintas, Carla, Bottillo, Irene, Sacco, Roberto, Azzarà, Alessia, Cassano, Ilaria, Ciccone, Maria Pia, Grammatico, Paola, Gurrieri, Fiorella
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9778367/
https://www.ncbi.nlm.nih.gov/pubmed/36553533
http://dx.doi.org/10.3390/genes13122266
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author Lintas, Carla
Bottillo, Irene
Sacco, Roberto
Azzarà, Alessia
Cassano, Ilaria
Ciccone, Maria Pia
Grammatico, Paola
Gurrieri, Fiorella
author_facet Lintas, Carla
Bottillo, Irene
Sacco, Roberto
Azzarà, Alessia
Cassano, Ilaria
Ciccone, Maria Pia
Grammatico, Paola
Gurrieri, Fiorella
author_sort Lintas, Carla
collection PubMed
description As a consequence of the implementation of NGS technologies, the diagnostic yield of neurodevelopmental disorders has dramatically increased during the past two decades. Among neurodevelopmental genes, transcription-related genes and chromatin remodeling genes are the most represented category of disease-causing genes. Indeed, the term “chromatinopathies” is now widely used to describe epigenetic disorders caused by mutations in these genes. We hereby describe a twenty-seven-year-old female patient diagnosed with moderate intellectual disability comorbid with other neuropsychiatric and behavioral issues carrying a de novo heterozygous stop variant in the KDM5C gene (NM_004187.5: c. 3847G>T, p.Glu1283*), encoding a histone demethylase that specifically acts on the H3K4 lysines. The gene is located on the X chromosome and has been associated with Claes–Jensen-type intellectual disability, an X-linked syndromic disorder. We discuss our case in relation to previously reported affected females harboring pathogenic mutations in the KDM5C gene with the objective of delineating genotype–phenotype correlations and further defining a common recognizable phenotype. We also highlight the importance of reverse phenotyping in relation to whole-exome sequencing results.
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spelling pubmed-97783672022-12-23 Expanding the Spectrum of KDM5C Neurodevelopmental Disorder: A Novel De Novo Stop Variant in a Young Woman and Emerging Genotype–Phenotype Correlations Lintas, Carla Bottillo, Irene Sacco, Roberto Azzarà, Alessia Cassano, Ilaria Ciccone, Maria Pia Grammatico, Paola Gurrieri, Fiorella Genes (Basel) Article As a consequence of the implementation of NGS technologies, the diagnostic yield of neurodevelopmental disorders has dramatically increased during the past two decades. Among neurodevelopmental genes, transcription-related genes and chromatin remodeling genes are the most represented category of disease-causing genes. Indeed, the term “chromatinopathies” is now widely used to describe epigenetic disorders caused by mutations in these genes. We hereby describe a twenty-seven-year-old female patient diagnosed with moderate intellectual disability comorbid with other neuropsychiatric and behavioral issues carrying a de novo heterozygous stop variant in the KDM5C gene (NM_004187.5: c. 3847G>T, p.Glu1283*), encoding a histone demethylase that specifically acts on the H3K4 lysines. The gene is located on the X chromosome and has been associated with Claes–Jensen-type intellectual disability, an X-linked syndromic disorder. We discuss our case in relation to previously reported affected females harboring pathogenic mutations in the KDM5C gene with the objective of delineating genotype–phenotype correlations and further defining a common recognizable phenotype. We also highlight the importance of reverse phenotyping in relation to whole-exome sequencing results. MDPI 2022-12-01 /pmc/articles/PMC9778367/ /pubmed/36553533 http://dx.doi.org/10.3390/genes13122266 Text en © 2022 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
Lintas, Carla
Bottillo, Irene
Sacco, Roberto
Azzarà, Alessia
Cassano, Ilaria
Ciccone, Maria Pia
Grammatico, Paola
Gurrieri, Fiorella
Expanding the Spectrum of KDM5C Neurodevelopmental Disorder: A Novel De Novo Stop Variant in a Young Woman and Emerging Genotype–Phenotype Correlations
title Expanding the Spectrum of KDM5C Neurodevelopmental Disorder: A Novel De Novo Stop Variant in a Young Woman and Emerging Genotype–Phenotype Correlations
title_full Expanding the Spectrum of KDM5C Neurodevelopmental Disorder: A Novel De Novo Stop Variant in a Young Woman and Emerging Genotype–Phenotype Correlations
title_fullStr Expanding the Spectrum of KDM5C Neurodevelopmental Disorder: A Novel De Novo Stop Variant in a Young Woman and Emerging Genotype–Phenotype Correlations
title_full_unstemmed Expanding the Spectrum of KDM5C Neurodevelopmental Disorder: A Novel De Novo Stop Variant in a Young Woman and Emerging Genotype–Phenotype Correlations
title_short Expanding the Spectrum of KDM5C Neurodevelopmental Disorder: A Novel De Novo Stop Variant in a Young Woman and Emerging Genotype–Phenotype Correlations
title_sort expanding the spectrum of kdm5c neurodevelopmental disorder: a novel de novo stop variant in a young woman and emerging genotype–phenotype correlations
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9778367/
https://www.ncbi.nlm.nih.gov/pubmed/36553533
http://dx.doi.org/10.3390/genes13122266
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