Reverse genotyping: unveiling Alu element insertion as a new cause of Kabuki syndrome using DNA methylation signature

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

doi:10.1186/s13148-025-01879-z

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Reverse genotyping: unveiling Alu element insertion as a new cause of Kabuki syndrome using DNA methylation signature

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Reverse genotyping: unveiling Alu element insertion as a new cause of Kabuki syndrome using DNA methylation signature

Quentin Sabbagh, Nathalie Ruiz-Pallares, Cassandra Rastin, Jacques Puechberty, Thomas Guignard, Claire Jeandel, Fanny Merklen, Pascal Pujol, Jennifer Kerkhof, Bekim Sadikovic, …

Clinical epigenetics, Vol.17(1), pp.69-6

29/04/2025

DOI: https://doi.org/10.1186/s13148-025-01879-z

PMID: 40301896

Résumé

Abnormalities, Multiple - diagnosis

Abnormalities, Multiple - genetics

Alu Elements - genetics

DNA Methylation - genetics

DNA-Binding Proteins - genetics

Face - abnormalities

Genotyping Techniques - methods

Hematologic Diseases - diagnosis

Hematologic Diseases - genetics

Humans

Neoplasm Proteins - genetics

Retrospective Studies

Vestibular Diseases - diagnosis

Vestibular Diseases - genetics

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.

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Titre: Reverse genotyping: unveiling Alu element insertion as a new cause of Kabuki syndrome using DNA methylation signature
Créateurs - sans rôle: Quentin Sabbagh - French Society for Predictive and Personalized Medicine (SFMPP), Montpellier, France
Nathalie Ruiz-Pallares - Department of Molecular Genetics and Cytogenomics, University Hospital of Montpellier, Montpellier University, Montpellier, France
Cassandra Rastin - Verspeeten Clinical Genome Centre, London Health Sciences Centre, London, ON, N6A 5W9, Canada
Jacques Puechberty - Department of Clinical Genetics, Centre de Référence « Anomalies du Développement et Syndromes Malformatifs », University Hospital of Montpellier, Inserm UMR1183, Montpellier University, Montpellier, France
Thomas Guignard - Department of Molecular Genetics and Cytogenomics, University Hospital of Montpellier, Montpellier University, Montpellier, France
Claire Jeandel - Department of Paediatric Endocrinology, University Hospital of Montpellier, Montpellier University, Montpellier, France
Fanny Merklen - Department of Otorhinolaryngology, University Hospital of Montpellier, Montpellier University, Montpellier, France
Pascal Pujol - Department of Cancer Genetics, University Hospital of Montpellier, UMR IRD 224-CNRS 5290, Montpellier University, Montpellier, France
Jennifer Kerkhof - London Health Sciences Centre
Bekim Sadikovic - London Health Sciences Centre
Mouna Barat-Houari - Department of Molecular Genetics and Cytogenomics, University Hospital of Montpellier, Montpellier University, Montpellier, France
David Geneviève - French Society for Predictive and Personalized Medicine (SFMPP), Montpellier, France. d-genevieve@chu-montpellier.fr
Détails de publication: Clinical epigenetics, Vol.17(1), pp.69-6
Identifiants: 99141108709311
Unité académique: Cell souches plasticité cellul régénérat tissulaire immuno des maladies inflamm - IRMB; Maladies Infectieuses et Vecteurs : Ecologie, Génétique, Evolution et Contrôle - MIVEGEC
Langue: English
Type de ressource: Journal article