{
  "abstract": "Fabry disease (FD) is the most common lysosomal storage disorder in which a severe, classical phenotype as well as a milder, non-classical phenotype can be distinguished. In this study we investigated the impact of the introduction of broader DNA sequencing techniques and subsequently the addition of the GLA-gene to NGS or WES based panels on the type of FD patient that is diagnosed by analyzing changes in the composition of the Dutch Fabry cohort over time. The current study confirms that Fabry disease is a genetically heterogeneous disorder with 64 different GLA variants established in a cohort of 319 patients. The introduction of broader DNA sequencing techniques, applied to a broader range of individuals with less specific symptoms, results in the identification of a higher proportion of individuals with less deleterious GLA variants and consequently a milder clinical phenotype. For the majority of individuals identified using the broader sequencing techniques cardiomyopathy is the presenting and only symptom of the disorder, in contrast to the multisystem classical Fabry disease phenotype. This phenotypic shift should be taken into account when comparing current to historical clinical and treatment effect data and requires tailored genetic counseling and clinical follow-up to prevent both over- and undertreatment.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Endocrinology and Metabolism, Amsterdam UMC, Amsterdam Gastroenterology Endocrinology Metabolism (AGEM) Research Institute, University of Amsterdam, Amsterdam, The Netherlands",
    "Department of Clinical Genetics, Maastricht University Medical Center, Maastricht, The Netherlands",
    "Department of Clinical Genetics, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands"
  ],
  "article_type": "Research Article",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Laura van Dussen"
    },
    {
      "affs": [
        1
      ],
      "name": "Emilie V. Albers"
    },
    {
      "affs": [
        2
      ],
      "name": "Saskia N. van der Crabben"
    },
    {
      "name": "Ronald H. Lekanne Deprez"
    },
    {
      "name": "Astrid S. Plomp"
    },
    {
      "name": "Mirjam Langeveld"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/erw2870bsgjc6.bib",
  "cited_by": 0,
  "doi": "10.1371/journal.pone.0358572",
  "fulltext_url": null,
  "id": "erw2870bsgjc6",
  "issns": [
    "1932-6203"
  ],
  "landing_url": "https://doi.org/10.1371/journal.pone.0358572",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2737|Lysosomal Storage Disorders Research"
    ],
    [
      "plos",
      "/Biology and life sciences/Computational biology/Genome analysis/Transcriptome analysis/Next-generation sequencing"
    ],
    [
      "plos",
      "/Biology and life sciences/Genetics/Gene identification and analysis/Genetic screens"
    ],
    [
      "plos",
      "/Biology and life sciences/Genetics/Genomics/Genome analysis/Transcriptome analysis/Next-generation sequencing"
    ],
    [
      "plos",
      "/Biology and life sciences/Genetics/Genomics/Genomic medicine/Genetic testing"
    ],
    [
      "plos",
      "/Biology and life sciences/Genetics/Human genetics"
    ],
    [
      "plos",
      "/Biology and life sciences/Genetics/Human genetics/Genetic testing"
    ],
    [
      "plos",
      "/Biology and life sciences/Genetics/Phenotypes"
    ],
    [
      "plos",
      "/Biology and life sciences/Molecular biology/Molecular biology techniques/Sequencing techniques/DNA sequencing"
    ],
    [
      "plos",
      "/Biology and life sciences/Molecular biology/Molecular biology techniques/Sequencing techniques/DNA sequencing/Next-generation sequencing"
    ],
    [
      "plos",
      "/Medicine and health sciences/Cardiology/Cardiovascular medicine/Cardiovascular diseases/Cardiomyopathies"
    ],
    [
      "plos",
      "/Medicine and health sciences/Clinical genetics/Genetic diseases/Fabry disease"
    ],
    [
      "plos",
      "/Medicine and health sciences/Clinical genetics/Genetic testing"
    ],
    [
      "plos",
      "/Medicine and health sciences/Medical conditions/Cardiovascular diseases/Cardiomyopathies"
    ],
    [
      "plos",
      "/Medicine and health sciences/Medical conditions/Genetic diseases/Fabry disease"
    ],
    [
      "plos",
      "/Research and analysis methods/Molecular biology techniques/Sequencing techniques/DNA sequencing"
    ],
    [
      "plos",
      "/Research and analysis methods/Molecular biology techniques/Sequencing techniques/DNA sequencing/Next-generation sequencing"
    ]
  ],
  "openalex": "W7213415958",
  "pdf_url": "https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0358572&type=printable",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-16",
  "publisher": "Public Library of Science",
  "ris": "https://research.draconitic.com/paper/erw2870bsgjc6.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:49Z",
      "native_id": "10.1371/journal.pone.0358572",
      "source": "plos",
      "url": "https://doi.org/10.1371/journal.pone.0358572"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "plos:molecular biology",
      "subfield": "molecular-biology"
    },
    {
      "field": "biology",
      "origin": "plos:genetics",
      "subfield": "genetics-genomics"
    },
    {
      "field": "medicine",
      "origin": "plos:human genetics",
      "subfield": "human-genetics"
    }
  ],
  "title": "The changing landscape of Fabry disease: Impact of the inclusion of the GLA-gene in broader NGS or WES based panels on the phenotypic spectrum",
  "title_text": "The changing landscape of Fabry disease: Impact of the inclusion of the GLA-gene in broader NGS or WES based panels on the phenotypic spectrum",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:49Z",
  "url": "https://research.draconitic.com/paper/erw2870bsgjc6",
  "venue": "PLOS One",
  "versions": []
}