Nature Communications (Jul 2024)
A CCG expansion in ABCD3 causes oculopharyngodistal myopathy in individuals of European ancestry
- Andrea Cortese,
- Sarah J. Beecroft,
- Stefano Facchini,
- Riccardo Curro,
- Macarena Cabrera-Serrano,
- Igor Stevanovski,
- Sanjog R. Chintalaphani,
- Hasindu Gamaarachchi,
- Ben Weisburd,
- Chiara Folland,
- Gavin Monahan,
- Carolin K. Scriba,
- Lein Dofash,
- Mridul Johari,
- Bianca R. Grosz,
- Melina Ellis,
- Liam G. Fearnley,
- Rick Tankard,
- Justin Read,
- Ashirwad Merve,
- Natalia Dominik,
- Elisa Vegezzi,
- Ricardo P. Schnekenberg,
- Gorka Fernandez-Eulate,
- Marion Masingue,
- Diane Giovannini,
- Martin B. Delatycki,
- Elsdon Storey,
- Mac Gardner,
- David J. Amor,
- Garth Nicholson,
- Steve Vucic,
- Robert D. Henderson,
- Thomas Robertson,
- Jason Dyke,
- Vicki Fabian,
- Frank Mastaglia,
- Mark R. Davis,
- Marina Kennerson,
- OPDM study group,
- Ros Quinlivan,
- Simon Hammans,
- Arianna Tucci,
- Melanie Bahlo,
- Catriona A. McLean,
- Nigel G. Laing,
- Tanya Stojkovic,
- Henry Houlden,
- Michael G. Hanna,
- Ira W. Deveson,
- Paul J. Lockhart,
- Phillipa J. Lamont,
- Michael C. Fahey,
- Enrico Bugiardini,
- Gianina Ravenscroft
Affiliations
- Andrea Cortese
- Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology
- Sarah J. Beecroft
- Pawsey Supercomputing Research Centre
- Stefano Facchini
- Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology
- Riccardo Curro
- Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology
- Macarena Cabrera-Serrano
- Harry Perkins Institute of Medical Research
- Igor Stevanovski
- Genomics and Inherited Disease Program, Garvan Institute of Medical Research
- Sanjog R. Chintalaphani
- Genomics and Inherited Disease Program, Garvan Institute of Medical Research
- Hasindu Gamaarachchi
- Genomics and Inherited Disease Program, Garvan Institute of Medical Research
- Ben Weisburd
- Program in Medical and Population Genetics, Broad Institute of MIT and Harvard
- Chiara Folland
- Harry Perkins Institute of Medical Research
- Gavin Monahan
- Harry Perkins Institute of Medical Research
- Carolin K. Scriba
- Harry Perkins Institute of Medical Research
- Lein Dofash
- Harry Perkins Institute of Medical Research
- Mridul Johari
- Harry Perkins Institute of Medical Research
- Bianca R. Grosz
- Northcott Neuroscience Laboratory, ANZAC Research Institute
- Melina Ellis
- Northcott Neuroscience Laboratory, ANZAC Research Institute
- Liam G. Fearnley
- Population Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, 1 G Royal Parade
- Rick Tankard
- Department of Mathematics and Statistics, Curtin University
- Justin Read
- Bruce Lefroy Centre, Murdoch Children’s Research Institute
- Ashirwad Merve
- Department of Neuropathology, National Hospital for Neurology and Neurosurgery
- Natalia Dominik
- Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology
- Elisa Vegezzi
- IRCCS Mondino Foundation
- Ricardo P. Schnekenberg
- Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology
- Gorka Fernandez-Eulate
- Centre de Référence des Maladies Neuromusculaires Nord-Est-Ile de France, Hôpital Pitié-Salpêtrière, Institut de Myologie, APHP
- Marion Masingue
- Centre de Référence des Maladies Neuromusculaires Nord-Est-Ile de France, Hôpital Pitié-Salpêtrière, Institut de Myologie, APHP
- Diane Giovannini
- CHU Grenoble Alpes, Grenoble Institut Neurosciences, INSERM, U1216, Université Grenoble Alpes
- Martin B. Delatycki
- Bruce Lefroy Centre, Murdoch Children’s Research Institute
- Elsdon Storey
- Neurology Department, The Alfred Hospital
- Mac Gardner
- The Laboratory for Genomic Medicine, University of Otago
- David J. Amor
- Bruce Lefroy Centre, Murdoch Children’s Research Institute
- Garth Nicholson
- Northcott Neuroscience Laboratory, ANZAC Research Institute
- Steve Vucic
- Faculty of Medicine and Health, University of Sydney
- Robert D. Henderson
- Department of Neurology, Royal Brisbane & Women’s Hospital
- Thomas Robertson
- Pathology Queensland, Royal Brisbane and Women’s Hospital
- Jason Dyke
- PathWest Neuropathology, Royal Perth Hospital
- Vicki Fabian
- PathWest Neuropathology, Royal Perth Hospital
- Frank Mastaglia
- Perron Institute for Neurological and Translational Science
- Mark R. Davis
- Neurogenetics Unit, Diagnostic Genomics, PathWest
- Marina Kennerson
- Northcott Neuroscience Laboratory, ANZAC Research Institute
- OPDM study group
- Ros Quinlivan
- Dubowitz Neuromuscular Centre, UCL Great Ormond Street Institute of Child Health & MRC Centre for Neuromuscular Diseases
- Simon Hammans
- Wessex Neurological Centre, University Hospital Southampton
- Arianna Tucci
- Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology
- Melanie Bahlo
- Population Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, 1 G Royal Parade
- Catriona A. McLean
- Department of Medical Biology, The University of Melbourne, Parkville
- Nigel G. Laing
- Harry Perkins Institute of Medical Research
- Tanya Stojkovic
- Centre de Référence des Maladies Neuromusculaires Nord-Est-Ile de France, Hôpital Pitié-Salpêtrière, Institut de Myologie, APHP
- Henry Houlden
- Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology
- Michael G. Hanna
- Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology
- Ira W. Deveson
- Genomics and Inherited Disease Program, Garvan Institute of Medical Research
- Paul J. Lockhart
- Bruce Lefroy Centre, Murdoch Children’s Research Institute
- Phillipa J. Lamont
- Neurogenetics Unit, Royal Perth Hospital
- Michael C. Fahey
- Department of Paediatrics Monash Children’s Hospital
- Enrico Bugiardini
- Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology
- Gianina Ravenscroft
- Harry Perkins Institute of Medical Research
- DOI
- https://doi.org/10.1038/s41467-024-49950-2
- Journal volume & issue
-
Vol. 15,
no. 1
pp. 1 – 15
Abstract
Abstract Oculopharyngodistal myopathy (OPDM) is an inherited myopathy manifesting with ptosis, dysphagia and distal weakness. Pathologically it is characterised by rimmed vacuoles and intranuclear inclusions on muscle biopsy. In recent years CGG • CCG repeat expansion in four different genes were identified in OPDM individuals in Asian populations. None of these have been found in affected individuals of non-Asian ancestry. In this study we describe the identification of CCG expansions in ABCD3, ranging from 118 to 694 repeats, in 35 affected individuals across eight unrelated OPDM families of European ancestry. ABCD3 transcript appears upregulated in fibroblasts and skeletal muscle from OPDM individuals, suggesting a potential role of over-expression of CCG repeat containing ABCD3 transcript in progressive skeletal muscle degeneration. The study provides further evidence of the role of non-coding repeat expansions in unsolved neuromuscular diseases and strengthens the association between the CGG • CCG repeat motif and a specific pattern of muscle weakness.
