Project Title
Identification of common and rare genomic factors in Chilean epilepsy patients
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Internal ID
1221464
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    Item type:Publication,
    Data-driven historical characterization of epilepsy-associated genes
    (2023)
    Marie Macnee
    ;
    PEREZ PALMA, EDUARDO ESTEBAN  
    ;
    Javier A. LĂłpez-Rivera
    ;
    Alina Ivaniuk
    ;
    Patrick May
      1  1Scopus© Citations 28
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    Item type:Publication,
    SCN9A should not be considered an epilepsy gene; Refuting a gene-disease association
    (Wiley, 2025-06-10)
    Ismael Ghanty
    ;
    PEREZ PALMA, EDUARDO ESTEBAN  
    ;
    Camilo Villaman
    ;
    Daniel Stobo
    ;
    Joseph Symonds
    Objective The SCN9A gene is primarily expressed in nociceptive pathways within the peripheral nervous system, and pathogenic variants are associated with human pain disorders. In recent years, several studies have proposed SCN9A as a monogenic cause of epilepsy. Our objective was to critically appraise the SCN9A–epilepsy gene–disease relationship. Methods We assessed “epilepsy-associated” SCN9A variants from four sources: (1) the literature up to December 2023 (n = 27), (2) epilepsy patients referred for genetic testing at a regional service in Glasgow, UK over a 5-year period (n = 30), (3) the Human Genetics Mutation Database (n = 25), and (4) ClinVar (n = 1546). The latter two are genome-wide variant databases, accepting submissions from genetic laboratories and research groups. We checked whether each SCN9A variant is present in the Genome Aggregation Database (gnomAD) V4 (a reference population database for variant interpretation), and classified its pathogenicity based on the American College of Molecular Genetics and Genomics/Association of Molecular Pathologists guidelines. Results Only three SCN9A variants were classified as “likely pathogenic,” of which two were identified in healthy individuals in gnomAD. A total of 1540 of the 1546 SCN9A variants in ClinVar labeled as being associated with epilepsy were also reported in association with hereditary sensory and autonomic neuropathy. No further clinical data were provided in 1482 of these submissions. Significance There is no convincing genetic evidence to support SCN9A as a causative epilepsy gene. As such, the inclusion of SCN9A in epilepsy genetic testing panels should be reassessed. Research centers and genetic testing laboratories should be rigorous and consistent in their submissions to variant databases.
    Scopus© Citations 3  4
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    Polygenic score analysis identifies distinct genetic risk profiles in Alzheimer’s disease comorbidities
    (Springer Science and Business Media LLC, 2025-04-03)
    Carlos F. Hernández
    ;
    Camilo Villaman
    ;
    Costin Leu
    ;
    Dennis Lal
    ;
    Ignacio Mata
      4
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    CNV-ClinViewer: enhancing the clinical interpretation of large copy-number variants online
    (2023)
    Marie Macnee
    ;
    Eduardo PĂ©rez-Palma
    ;
    Tobias BrĂĽnger
    ;
    Chiara Klöckner
    ;
    Konrad Platzer
    <jats:title>Abstract</jats:title> <jats:sec> <jats:title>Motivation</jats:title> <jats:p>Pathogenic copy-number variants (CNVs) can cause a heterogeneous spectrum of rare and severe disorders. However, most CNVs are benign and are part of natural variation in human genomes. CNV pathogenicity classification, genotype–phenotype analyses, and therapeutic target identification are challenging and time-consuming tasks that require the integration and analysis of information from multiple scattered sources by experts.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>Here, we introduce the CNV-ClinViewer, an open-source web application for clinical evaluation and visual exploration of CNVs. The application enables real-time interactive exploration of large CNV datasets in a user-friendly designed interface and facilitates semi-automated clinical CNV interpretation following the ACMG guidelines by integrating the ClassifCNV tool. In combination with clinical judgment, the application enables clinicians and researchers to formulate novel hypotheses and guide their decision-making process. Subsequently, the CNV-ClinViewer enhances for clinical investigators’ patient care and for basic scientists’ translational genomic research.</jats:p> </jats:sec> <jats:sec> <jats:title>Availability and implementation</jats:title> <jats:p>The web application is freely available at https://cnv-ClinViewer.broadinstitute.org and the open-source code can be found at https://github.com/LalResearchGroup/CNV-clinviewer.</jats:p> </jats:sec>
    Scopus© Citations 13  15