Department of Genetics, School of Medicine, University of North Carolina at Chapel Hill, NC, USA.
American College of Medical Genetics and Genomics, Bethesda, MD, USA.
Mol Genet Metab. 2023 Jul;139(3):107604. doi: 10.1016/j.ymgme.2023.107604. Epub 2023 May 11.
Peroxisomal disorders are heterogeneous in nature, with phenotypic overlap that is indistinguishable without molecular testing. Newborn screening and gene sequencing for a panel of genes implicated in peroxisomal diseases are critical tools for the early and accurate detection of these disorders. It is therefore essential to evaluate the clinical validity of the genes included in sequencing panels for peroxisomal disorders. The Peroxisomal Gene Curation Expert Panel (GCEP) assessed genes frequently included on clinical peroxisomal testing panels using the Clinical Genome Resource (ClinGen) gene-disease validity curation framework and classified gene-disease relationships as Definitive, Strong, Moderate, Limited, Disputed, Refuted, or No Known Disease Relationship. Subsequent to gene curation, the GCEP made recommendations to update the disease nomenclature and ontology in the Monarch Disease Ontology (Mondo) database. Thirty-six genes were assessed for the strength of evidence supporting their role in peroxisomal disease, leading to 36 gene-disease relationships, after two genes were removed for their lack of a role in peroxisomal disease and two genes were curated for two different disease entities each. Of these, 23 were classified as Definitive (64%), one as Strong (3%), eight as Moderate (23%), two as Limited (5%), and two as No known disease relationship (5%). No contradictory evidence was found to classify any relationships as Disputed or Refuted. The gene-disease relationship curations are publicly available on the ClinGen website (https://clinicalgenome.org/affiliation/40049/). The changes to peroxisomal disease nomenclature are displayed on the Mondo website (http://purl.obolibrary.org/obo/MONDO_0019053). The Peroxisomal GCEP-curated gene-disease relationships will inform clinical and laboratory diagnostics and enhance molecular testing and reporting. As new data will emerge, the gene-disease classifications asserted by the Peroxisomal GCEP will be re-evaluated periodically.
过氧化物酶体疾病在性质上具有异质性，表型重叠，如果没有分子检测，是无法区分的。新生儿筛查和针对过氧化物酶体疾病相关基因的基因测序是早期准确检测这些疾病的关键工具。因此，评估过氧化物酶体疾病测序组中包含的基因的临床有效性至关重要。过氧化物酶体基因审核专家小组 (GCEP) 使用临床基因组资源 (ClinGen) 基因-疾病有效性审核框架评估了临床过氧化物酶体检测中经常包含的基因，并将基因-疾病关系分类为明确、强、中等、有限、有争议、反驳或无已知疾病关系。基因审核后，GCEP 建议更新 Monarch 疾病本体 (Mondo) 数据库中的疾病命名法和本体论。在删除了两个缺乏过氧化物酶体疾病作用的基因和两个分别为两个不同疾病实体审核的基因后，对 36 个基因进行了评估，以支持其在过氧化物酶体疾病中的作用的证据强度，共得出 36 个基因-疾病关系。其中，23 个被归类为明确 (64%)，1 个为强 (3%)，8 个为中等 (23%)，2 个为有限 (5%)，2 个为无已知疾病关系 (5%)。没有发现矛盾的证据将任何关系归类为有争议或反驳。基因-疾病关系审核可在 ClinGen 网站 (https://clinicalgenome.org/affiliation/40049/) 上公开获取。过氧化物酶体疾病命名法的变化显示在 Mondo 网站 (http://purl.obolibrary.org/obo/MONDO_0019053) 上。过氧化物酶体 GCEP 审核的基因-疾病关系将为临床和实验室诊断提供信息，并增强分子检测和报告。随着新数据的出现，过氧化物酶体 GCEP 断言的基因-疾病分类将定期重新评估。
