Clinical validity of congenital myopathy genes determined by the ClinGen Congenital Myopathies Expert Panel-Reference-Cited by-同舟云学术

Clinical validity of congenital myopathy genes determined by the ClinGen Congenital Myopathies Expert Panel

Published:2025-06-10 Issue: Volume: Page:
ISSN:2214-3599
Container-title:Journal of Neuromuscular Diseases
language:en
Short-container-title:Journal of Neuromuscular Diseases

Author:

Ross Justyne E¹^ORCID,Flowers May¹,McNulty Shannon¹^ORCID,Patel Mayher²,Yang Hui³,Palus Brooke¹,Abdelmoneim Elnagheeb Marwa¹,Eng Lucy¹^ORCID,Owens Emma¹,Beggs Alan H⁴^ORCID,Bertini Enrico⁵^ORCID,D'Amico Adele⁵,Donkervoort Sandra⁶,Dowling James⁷,Fattori Fabiana⁵,Ferreiro Ana⁸,Genetti Casie A⁴^ORCID,Gonorazky Hernan⁸,Lek Monkol⁹,Lindy Amanda³,Medne Livija¹⁰^ORCID,Muntoni Francesco¹¹^ORCID,Pajusalu Sander⁹¹²¹³,Pelin Katarina¹⁴^ORCID,Rendu John¹⁵,Sarkozy Anna¹¹,Vatta Matteo¹⁶^ORCID,Winder Tom¹⁶,Yoon Grace¹⁷^ORCID,Bönnemann Carsten G⁶,Ceyhan-Birsoy Ozge¹⁸

Affiliation:

1. Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

2. The Broad Institute of MIT and Harvard, Cambridge, MA, USA

3. GeneDx, Gaithersburg, MD, USA

4. Division of Genetics and Genomics, The Manton Center for Orphan Disease Research, Boston Children's Hospital, and Department of Pediatrics, Harvard Medical School, Boston, MA, USA

5. Unit of Neuromuscular and Neurodegenerative Disorders, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy

6. Neuromuscular and Neurogenetic Disorders of Childhood Section, NIH, National Institute of Neurological Disorders, Bethesda, USA

7. Division of Neurology, Program for Genetics and Genome Biology, Hospital for Sick Children, Toronto, Canada

8. Basic and Translational Myology Laboratory, Université de Paris, Paris, France

9. Department of Genetics, Yale School of Medicine, New Haven, USA

10. Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, USA

11. Dubowitz Neuromuscular Centre, University College London Great Ormond Street Institute of Child Health, London, UK

12. Department of Clinical Genetics, Institute of Clinical Medicine, University of Tartu, Tartu, Estonia

13. Genetic and Personalized Medicine Clinic, Tartu University Hospital, Tartu, Estonia

14. Molecular and Integrative Biosciences Research Programme, Faculty of Biological and Environmental Sciences, University of Helsinki, Helsinki, Finland

15. Univ. Grenoble Alpes, Inserm, U1216, CHU Grenoble Alpes, Grenoble Institut Neurosciences, Grenoble, France

16. Labcorp Genetics Inc. (formerly Invitae Corp.), San Francisco, CA, USA

17. Divisions of Neurology and Clinical and Metabolic Genetics, Department of Pediatrics, University of Toronto, The Hospital for Sick Children, Toronto, Canada

18. Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA

Abstract

Background: Congenital myopathies are a group of neuromuscular disorders that typically present at birth or early childhood with hypotonia and non-progressive or slowly progressive muscle weakness. They are classically subclassified by characteristic structural changes and histopathological findings in skeletal muscle. Variants in over 40 genes have been described to date in patients with various forms of congenital myopathy with overlapping phenotypic and histological features, which poses a challenge for laboratories and clinicians in interpreting genetic findings. Objective: The purpose of this study was to evaluate the evidence supporting each gene-disease relationship and provide an expert-reviewed classification for the clinical validity of genes involved in congenital myopathies. Methods: The ClinGen Neurological Disorders Clinical Domain Working Group assembled the Congenital Myopathies Gene Curation Expert Panel (CongenMyopathy-GCEP), a group of clinicians and geneticists with expertise in congenital myopathies tasked to perform evidence-based curation of 50 gene-disease relationships using the ClinGen semiquantitative framework to assign clinical validity. Results: Our curation effort resulted in 35 (70%) Definitive, eight (16%) Moderate, six (12%) Limited, and one (2%) Disputed disease relationship classifications. The summary of each curation is made publicly available on the ClinGen website. Conclusions: Expert-reviewed assignment of gene-disease relationships by the CongenMyopathy-GCEP facilitates accurate molecular diagnoses for congenital myopathies and can allow genetic testing to focus on genes with a validated role in disease.

Publisher

SAGE Publications

Link

https://journals.sagepub.com/doi/pdf/10.1177/22143602251339369

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