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ORIGINAL RESEARCH article

Front. Genet.
Sec. Genetics of Common and Rare Diseases
Volume 15 - 2024 | doi: 10.3389/fgene.2024.1472543
This article is part of the Research Topic Insights in Genetics of Common and Rare Diseases 2024 View all articles

An intragenic duplication in the AFF2 gene associated with Cornelia de Lange syndrome phenotype

Provisionally accepted
Cristina Lucia-Campos Cristina Lucia-Campos 1Ilaria Parenti Ilaria Parenti 2Ana Latorre-Pellicer Ana Latorre-Pellicer 1Marta Gil-Salvador Marta Gil-Salvador 1Ilaria Bestetti Ilaria Bestetti 3Palma Finelli Palma Finelli 3,4Lidia Larizza Lidia Larizza 5Maria Arnedo Maria Arnedo 1Ariadna Ayerza-Casas Ariadna Ayerza-Casas 1,6Julia Del Rincón Julia Del Rincón 1Laura Trujillano Laura Trujillano 1,7Beatriz Morte Beatriz Morte 8Luis A. Pérez-Jurado Luis A. Pérez-Jurado 10,8,9Pablo Lapunzina Pablo Lapunzina 11,12,8Elsa Leitão Elsa Leitão 2Jasmin Beygo Jasmin Beygo 2Christina Lich Christina Lich 2Fabian Kilpert Fabian Kilpert 2Sabine Kaya Sabine Kaya 2Christel Depienne Christel Depienne 2Frank J. Kaiser Frank J. Kaiser 13,2Feliciano J. Ramos Feliciano J. Ramos 14*Beatriz Puisac Beatriz Puisac 1*Juan Pié Juan Pié 1*
  • 1 Unit of Clinical Genetics and Functional Genomics, Department of Pharmacology and Physiology, School of Medicine, University of Zaragoza, CIBERER-GCV02 and IIS-Aragon, Zaragoza, Spain
  • 2 Institute of Human Genetics, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
  • 3 SC Clinical Pathology, SS Medical Genetics Laboratory, Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
  • 4 Department of Medical Biotechnology and Translational Medicine, Università degli Studi di Milano, Milan, Italy
  • 5 Experimental Research Laboratory of Medical Cytogenetics and Molecular Genetics, IRCCS Istituto Auxologico Italiano, Milan, Italy
  • 6 Unit of Paediatric Cardiology, Service of Paediatrics, University Hospital “Miguel Servet”, Zaragoza, Spain
  • 7 Department of Clinical and Molecular Genetics Hospital Vall d'Hebron, Barcelona, Spain
  • 8 Centre for Biomedical Network Research on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Madrid, Spain
  • 9 Genetics Service, Hospital del Mar Research Institute (IMIM), Barcelona, Spain
  • 10 Universitat Pompeu Fabra, Barcelona, Spain
  • 11 Institute of Medical and Molecular Genetics (INGEMM), University Hospital “La Paz”-IdiPAZ, Madrid, Spain
  • 12 ERN-ITHACA-European Reference Network, Paris, France
  • 13 Center for Rare Diseases (Essener Zentrum für Seltene Erkrankungen, EZSE), University Hospital Essen, Essen, Germany
  • 14 Unit of Clinical Genetics, Service of Paediatrics, Department of Paediatrics, University Hospital “Lozano Blesa”, School of Medicine, University of Zaragoza, CIBERER-GCV02 and IIS-Aragon, Zaragoza, Spain

The final, formatted version of the article will be published soon.

    We are submitting our manuscript for consideration as an article in Frontiers in Genetics. In this study, we report for the first time an intragenic duplication in the AFF2 gene related with classic Cornelia de Lange syndrome (CdLS) phenotype. We present phenotype data of the affected family members and assess the pathogenicity of the intragenic variant through a combination of clinical phenotype evaluation, clinical exome sequencing, high-resolution array-CGH, deep-sequencing CdLS gene panel, targeted sequencing with Oxford Nanopore Technologies (ONT), gene expression analysis and assessment of X chromosome. In addition, a systematic review of AFF2 variants and their clinical features was performanced. Significant efforts have been devoted to the genetic diagnostic of this case. This is the first time that the AFF2 gene has been linked to CdLS. In this article, the data have been given in chronological order to highlight the main challenge found in the clinical and molecular diagnos

    Keywords: Ariadna Ayerza-Casas: Investigation, methodology, Writing -review & editing. Ana Latorre-Pellicer: Investigation, Writing -review & editing. Beatriz Morte: Investigation, resources, Writing -review & editing. Christel Depienne: Investigation, Writing -review & editing. Christina Lich: Investigation, Writing -review & editing. Cristina Lucia-Campos: Conceptualization

    Received: 29 Jul 2024; Accepted: 11 Oct 2024.

    Copyright: © 2024 Lucia-Campos, Parenti, Latorre-Pellicer, Gil-Salvador, Bestetti, Finelli, Larizza, Arnedo, Ayerza-Casas, Del Rincón, Trujillano, Morte, Pérez-Jurado, Lapunzina, Leitão, Beygo, Lich, Kilpert, Kaya, Depienne, Kaiser, Ramos, Puisac and Pié. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Feliciano J. Ramos, Unit of Clinical Genetics, Service of Paediatrics, Department of Paediatrics, University Hospital “Lozano Blesa”, School of Medicine, University of Zaragoza, CIBERER-GCV02 and IIS-Aragon, Zaragoza, Spain
    Beatriz Puisac, Unit of Clinical Genetics and Functional Genomics, Department of Pharmacology and Physiology, School of Medicine, University of Zaragoza, CIBERER-GCV02 and IIS-Aragon, Zaragoza, Spain
    Juan Pié, Unit of Clinical Genetics and Functional Genomics, Department of Pharmacology and Physiology, School of Medicine, University of Zaragoza, CIBERER-GCV02 and IIS-Aragon, Zaragoza, Spain

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.