Reverse genotyping: unveiling Alu element insertion as a new cause of Kabuki syndrome using DNA methylation signature
Abstract Kabuki syndrome type 1 (KS1) is a monogenic disorder arising from pathogenic variants within KMT2D and characterized by syndromic neurodevelopmental delay. We report the retrospective identification of a causative AluY insertion within KMT2D in a genetically unsolved individual with typical...
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| Language: | English |
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BMC
2025-04-01
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| Series: | Clinical Epigenetics |
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| Online Access: | https://doi.org/10.1186/s13148-025-01879-z |
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| author | Quentin Sabbagh Nathalie Ruiz-Pallares Cassandra Rastin Jacques Puechberty Thomas Guignard Claire Jeandel Fanny Merklen Pascal Pujol Jennifer Kerkhof Bekim Sadikovic Mouna Barat-Houari David Geneviève |
| author_facet | Quentin Sabbagh Nathalie Ruiz-Pallares Cassandra Rastin Jacques Puechberty Thomas Guignard Claire Jeandel Fanny Merklen Pascal Pujol Jennifer Kerkhof Bekim Sadikovic Mouna Barat-Houari David Geneviève |
| author_sort | Quentin Sabbagh |
| collection | DOAJ |
| description | Abstract Kabuki syndrome type 1 (KS1) is a monogenic disorder arising from pathogenic variants within KMT2D and characterized by syndromic neurodevelopmental delay. We report the retrospective identification of a causative AluY insertion within KMT2D in a genetically unsolved individual with typical KS1 features, after identification of a DNA methylation signature. This is the first documentation of Alu insertion as a molecular mechanism responsible for KS1. This study emphasizes the need for reanalyzing inconclusive sequencing data in individuals with gene-specific phenotypes and reinforces episignature as a reliable diagnostic tool when NGS approaches fail to provide conclusive results in individuals with rare diseases. |
| format | Article |
| id | doaj-art-6deddf5dcb9043ceac01c8242013eead |
| institution | OA Journals |
| issn | 1868-7083 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Clinical Epigenetics |
| spelling | doaj-art-6deddf5dcb9043ceac01c8242013eead2025-08-20T02:10:49ZengBMCClinical Epigenetics1868-70832025-04-011711610.1186/s13148-025-01879-zReverse genotyping: unveiling Alu element insertion as a new cause of Kabuki syndrome using DNA methylation signatureQuentin Sabbagh0Nathalie Ruiz-Pallares1Cassandra Rastin2Jacques Puechberty3Thomas Guignard4Claire Jeandel5Fanny Merklen6Pascal Pujol7Jennifer Kerkhof8Bekim Sadikovic9Mouna Barat-Houari10David Geneviève11Department of Clinical Genetics, Centre de Référence « Anomalies du Développement et Syndromes Malformatifs », University Hospital of Montpellier, Inserm UMR1183, Montpellier UniversityDepartment of Molecular Genetics and Cytogenomics, University Hospital of Montpellier, Montpellier UniversityVerspeeten Clinical Genome Centre, London Health Sciences CentreDepartment of Clinical Genetics, Centre de Référence « Anomalies du Développement et Syndromes Malformatifs », University Hospital of Montpellier, Inserm UMR1183, Montpellier UniversityDepartment of Molecular Genetics and Cytogenomics, University Hospital of Montpellier, Montpellier UniversityDepartment of Paediatric Endocrinology, University Hospital of Montpellier, Montpellier UniversityDepartment of Otorhinolaryngology, University Hospital of Montpellier, Montpellier UniversityFrench Society for Predictive and Personalized Medicine (SFMPP)Verspeeten Clinical Genome Centre, London Health Sciences CentreVerspeeten Clinical Genome Centre, London Health Sciences CentreDepartment of Molecular Genetics and Cytogenomics, University Hospital of Montpellier, Montpellier UniversityDepartment of Clinical Genetics, Centre de Référence « Anomalies du Développement et Syndromes Malformatifs », University Hospital of Montpellier, Inserm UMR1183, Montpellier UniversityAbstract Kabuki syndrome type 1 (KS1) is a monogenic disorder arising from pathogenic variants within KMT2D and characterized by syndromic neurodevelopmental delay. We report the retrospective identification of a causative AluY insertion within KMT2D in a genetically unsolved individual with typical KS1 features, after identification of a DNA methylation signature. This is the first documentation of Alu insertion as a molecular mechanism responsible for KS1. This study emphasizes the need for reanalyzing inconclusive sequencing data in individuals with gene-specific phenotypes and reinforces episignature as a reliable diagnostic tool when NGS approaches fail to provide conclusive results in individuals with rare diseases.https://doi.org/10.1186/s13148-025-01879-zKabuki syndromeKMT2DEpigenetic signatureAlu elementMobile element insertion |
| spellingShingle | Quentin Sabbagh Nathalie Ruiz-Pallares Cassandra Rastin Jacques Puechberty Thomas Guignard Claire Jeandel Fanny Merklen Pascal Pujol Jennifer Kerkhof Bekim Sadikovic Mouna Barat-Houari David Geneviève Reverse genotyping: unveiling Alu element insertion as a new cause of Kabuki syndrome using DNA methylation signature Clinical Epigenetics Kabuki syndrome KMT2D Epigenetic signature Alu element Mobile element insertion |
| title | Reverse genotyping: unveiling Alu element insertion as a new cause of Kabuki syndrome using DNA methylation signature |
| title_full | Reverse genotyping: unveiling Alu element insertion as a new cause of Kabuki syndrome using DNA methylation signature |
| title_fullStr | Reverse genotyping: unveiling Alu element insertion as a new cause of Kabuki syndrome using DNA methylation signature |
| title_full_unstemmed | Reverse genotyping: unveiling Alu element insertion as a new cause of Kabuki syndrome using DNA methylation signature |
| title_short | Reverse genotyping: unveiling Alu element insertion as a new cause of Kabuki syndrome using DNA methylation signature |
| title_sort | reverse genotyping unveiling alu element insertion as a new cause of kabuki syndrome using dna methylation signature |
| topic | Kabuki syndrome KMT2D Epigenetic signature Alu element Mobile element insertion |
| url | https://doi.org/10.1186/s13148-025-01879-z |
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