Consensus recommendations for next-generation sequencing-based genetic testing in Rare Neurological diseases

Abstract We recently established an external quality assessment (EQA) scheme for next-generation sequencing (NGS) diagnostics in rare neurological disorders (RND) in collaboration with the EMQN. The first assessment rounds revealed limitations and variability in the quality and completeness of genetic testing reports. To improve and harmonize reporting in NGS-based diagnostics for RND, we identified 28 topics requiring recommendations based on EQA findings. These topics were grouped into four areas: clinical information, interpretation, methodology, and reporting. A team of 31 experts with relevant expertise was formed. Using an adapted Delphi approach, two rounds of surveys were conducted to prioritize the topics. Subsequently, area-specific expert groups met to formulate recommendations, followed by a final approval round using the five-finger consensus method involving all experts. In both Delphi rounds, all topics were rated as either very important ( n = 12) or important ( n = 16), and all were advanced for recommendation development. Consensus recommendations were achieved for 27 of the 28 topics. These include guidance on gene panel composition and updating, addressing disease-specific limitations of NGS (e.g., repeat expansion disorders), defining minimal quality parameters, and promoting sharing of variant interpretations. Each recommendation is supported by real-world examples. Due to differences in national healthcare frameworks and policies, consensus could not be reached regarding which patients should or should not undergo NGS testing. The dissemination of these recommendations is expected to improve the quality of genetic testing and reporting in RND diagnostics, promoting harmonization across laboratories and enabling easier comparison and interpretation of genetic testing reports.

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Publication Details

Journal
European Journal of Human Genetics
Published
2026-07-28
DOI
https://doi.org/10.1038/s41431-026-02198-4
Primary Topic
Genomics and Rare Diseases
Type
article
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article

Consensus recommendations for next-generation sequencing-based genetic testing in Rare Neurological diseases

Borut Peterlin, Kornelia Neveling, Katja Lohmann, Tobias B. Haack et al.
European Journal of Human Genetics
Genomics and Rare Diseases
article

Consensus recommendations for next-generation sequencing-based genetic testing in Rare Neurological diseases

Borut Peterlin, Kornelia Neveling, Katja Lohmann, Tobias B. Haack, Katie Sheils, Zih‐Hua Fang, Marina A.J. Tijssen, Lisenka E.L.M. Vissers, Nika Schuermans, Victoria Williams, Fran Borovečki, M Mancuso, Ivo Barić, Milena Janković, Sylvia Boesch, Norbert Brüggemann, Holm Graeßner, Deborah Mascalzoni, Rachel Taylor, Mária Judit Molnár, Henry Houlden, Marc Sturm, Peter Bauer, Astri Arnesen, Erik‐Jan Kamsteeg, Kailash P. Bhatia, Alexander Münchau, Ivana Novakovic, Aleš Maver, Heinz Gabriel, Ludger Schols, Lena-Marie Urbanczyk, on behalf of the European Reference Network for Rare Neurological Disorders (ERN-RND)
article en

Abstract

Abstract We recently established an external quality assessment (EQA) scheme for next-generation sequencing (NGS) diagnostics in rare neurological disorders (RND) in collaboration with the EMQN. The first assessment rounds revealed limitations and variability in the quality and completeness of genetic testing reports. To improve and harmonize reporting in NGS-based diagnostics for RND, we identified 28 topics requiring recommendations based on EQA findings. These topics were grouped into four areas: clinical information, interpretation, methodology, and reporting. A team of 31 experts with relevant expertise was formed. Using an adapted Delphi approach, two rounds of surveys were conducted to prioritize the topics. Subsequently, area-specific expert groups met to formulate recommendations, followed by a final approval round using the five-finger consensus method involving all experts. In both Delphi rounds, all topics were rated as either very important ( n = 12) or important ( n = 16), and all were advanced for recommendation development. Consensus recommendations were achieved for 27 of the 28 topics. These include guidance on gene panel composition and updating, addressing disease-specific limitations of NGS (e.g., repeat expansion disorders), defining minimal quality parameters, and promoting sharing of variant interpretations. Each recommendation is supported by real-world examples. Due to differences in national healthcare frameworks and policies, consensus could not be reached regarding which patients should or should not undergo NGS testing. The dissemination of these recommendations is expected to improve the quality of genetic testing and reporting in RND diagnostics, promoting harmonization across laboratories and enabling easier comparison and interpretation of genetic testing reports.

European Journal of Human Genetics
Semmelweis University (HU), University of Pisa (IT), Uppsala University (SE), University Medical Center Groningen (NL), University Hospital Centre Zagreb (HR), Innsbruck Medical University (AT), Radboud University Nijmegen (NL), University of Zagreb (HR), Ghent University Hospital (BE), Ljubljana University Medical Centre (SI), German Center for Neurodegenerative Diseases (DE), Radboud University Medical Center (NL), University of Belgrade (RS), Ion Exchange (India) (IN), Praxis für Humangenetik Tübingen (DE), Centogene (Germany) (DE), Hertie Institute for Clinical Brain Research (DE), STZ eyetrial (DE), National Hospital for Neurology and Neurosurgery (GB), University College London (GB), University of Tübingen (DE), University of Lübeck (DE)
Partnerships for the goals
Openalex Percentile: Top 8%
Genomics and Rare Diseases
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