Expanding the Spectrum of <i>KDM5C</i> 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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| Format: | Article |
| Language: | English |
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MDPI AG
2022-12-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/13/12/2266 |
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| author | Carla Lintas Irene Bottillo Roberto Sacco Alessia Azzarà Ilaria Cassano Maria Pia Ciccone Paola Grammatico Fiorella Gurrieri |
| author_facet | Carla Lintas Irene Bottillo Roberto Sacco Alessia Azzarà Ilaria Cassano Maria Pia Ciccone Paola Grammatico Fiorella Gurrieri |
| author_sort | Carla Lintas |
| collection | DOAJ |
| 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 <i>KDM5C</i> 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 <i>KDM5C</i> 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. |
| first_indexed | 2024-03-09T16:29:20Z |
| format | Article |
| id | doaj.art-4fe9e321f6de40fca55c5e2ccca643d1 |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-09T16:29:20Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-4fe9e321f6de40fca55c5e2ccca643d12023-11-24T15:03:54ZengMDPI AGGenes2073-44252022-12-011312226610.3390/genes13122266Expanding the Spectrum of <i>KDM5C</i> Neurodevelopmental Disorder: A Novel De Novo Stop Variant in a Young Woman and Emerging Genotype–Phenotype CorrelationsCarla Lintas0Irene Bottillo1Roberto Sacco2Alessia Azzarà3Ilaria Cassano4Maria Pia Ciccone5Paola Grammatico6Fiorella Gurrieri7Research Unit of Medical Genetics, Department of Medicine, Università Campus Bio-Medico di Roma, Via Alvaro del Portillo 21, 00128 Rome, ItalyDivision of Medical Genetics, Department of Experimental Medicine, San Camillo-Forlanini Hospital, Sapienza University, 00185 Rome, ItalyResearch Unit of Medical Genetics, Department of Medicine, Università Campus Bio-Medico di Roma, Via Alvaro del Portillo 21, 00128 Rome, ItalyResearch Unit of Medical Genetics, Department of Medicine, Università Campus Bio-Medico di Roma, Via Alvaro del Portillo 21, 00128 Rome, ItalyResearch Unit of Medical Genetics, Department of Medicine, Università Campus Bio-Medico di Roma, Via Alvaro del Portillo 21, 00128 Rome, ItalyDivision of Medical Genetics, Department of Experimental Medicine, San Camillo-Forlanini Hospital, Sapienza University, 00185 Rome, ItalyDivision of Medical Genetics, Department of Experimental Medicine, San Camillo-Forlanini Hospital, Sapienza University, 00185 Rome, ItalyResearch Unit of Medical Genetics, Department of Medicine, Università Campus Bio-Medico di Roma, Via Alvaro del Portillo 21, 00128 Rome, ItalyAs 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 <i>KDM5C</i> 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 <i>KDM5C</i> 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.https://www.mdpi.com/2073-4425/13/12/2266X-linked intellectual disabilityneuropsychiatric disorders<i>KDM5C</i> geneepigenetic signatureClaes–Jensen syndrome |
| spellingShingle | Carla Lintas Irene Bottillo Roberto Sacco Alessia Azzarà Ilaria Cassano Maria Pia Ciccone Paola Grammatico Fiorella Gurrieri Expanding the Spectrum of <i>KDM5C</i> Neurodevelopmental Disorder: A Novel De Novo Stop Variant in a Young Woman and Emerging Genotype–Phenotype Correlations Genes X-linked intellectual disability neuropsychiatric disorders <i>KDM5C</i> gene epigenetic signature Claes–Jensen syndrome |
| title | Expanding the Spectrum of <i>KDM5C</i> Neurodevelopmental Disorder: A Novel De Novo Stop Variant in a Young Woman and Emerging Genotype–Phenotype Correlations |
| title_full | Expanding the Spectrum of <i>KDM5C</i> Neurodevelopmental Disorder: A Novel De Novo Stop Variant in a Young Woman and Emerging Genotype–Phenotype Correlations |
| title_fullStr | Expanding the Spectrum of <i>KDM5C</i> Neurodevelopmental Disorder: A Novel De Novo Stop Variant in a Young Woman and Emerging Genotype–Phenotype Correlations |
| title_full_unstemmed | Expanding the Spectrum of <i>KDM5C</i> Neurodevelopmental Disorder: A Novel De Novo Stop Variant in a Young Woman and Emerging Genotype–Phenotype Correlations |
| title_short | Expanding the Spectrum of <i>KDM5C</i> Neurodevelopmental Disorder: A Novel De Novo Stop Variant in a Young Woman and Emerging Genotype–Phenotype Correlations |
| title_sort | expanding the spectrum of i kdm5c i neurodevelopmental disorder a novel de novo stop variant in a young woman and emerging genotype phenotype correlations |
| topic | X-linked intellectual disability neuropsychiatric disorders <i>KDM5C</i> gene epigenetic signature Claes–Jensen syndrome |
| url | https://www.mdpi.com/2073-4425/13/12/2266 |
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