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; 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; OPDM study group; Stephan L Zuchner

doi:10.1038/s41467-024-49950-2

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A CCG expansion in ABCD3 causes oculopharyngodistal myopathy in individuals of European ancestry

Journal article

Peer reviewed

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, …

Nature communications, Vol.15(1), pp.6327-15

2024-07-27

DOI: https://doi.org/10.1038/s41467-024-49950-2

PMID: 39068203

Appears in Miller School of Medicine - Latest Publications

Abstract

Adolescent

Adult

Aged

ATP-Binding Cassette Transporters - genetics

Female

Fibroblasts - metabolism

Fibroblasts - pathology

Humans

Male

Middle Aged

Muscle Weakness - genetics

Muscle Weakness - pathology

Muscle, Skeletal - pathology

Muscular Dystrophies

Myopathies, Structural, Congenital - genetics

Myopathies, Structural, Congenital - pathology

Pedigree

Trinucleotide Repeat Expansion

White People - genetics

Young Adult

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.

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Title: A CCG expansion in ABCD3 causes oculopharyngodistal myopathy in individuals of European ancestry
Creators: Andrea Cortese - National Hospital for Neurology and Neurosurgery
Sarah J Beecroft - Pawsey Supercomputing Research Centre
Stefano Facchini - National Hospital for Neurology and Neurosurgery
Riccardo Curro - National Hospital for Neurology and Neurosurgery
Macarena Cabrera-Serrano - Harry Perkins Institute of Medical Research
Igor Stevanovski - Garvan Institute of Medical Research
Sanjog R Chintalaphani - Garvan Institute of Medical Research
Hasindu Gamaarachchi - Garvan Institute of Medical Research
Ben Weisburd - Broad Institute
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 - Anzac Research Institute
Melina Ellis - Anzac Research Institute
Liam G Fearnley - Walter and Eliza Hall Institute of Medical Research
Rick Tankard - Curtin University
Justin Read - Murdoch Children's Research Institute
Ashirwad Merve - National Hospital for Neurology and Neurosurgery
Natalia Dominik - University College London
Elisa Vegezzi - IRCCS Mondino Foundation, Pavia, Italy
Ricardo P Schnekenberg - University of Pavia
Gorka Fernandez-Eulate - Institut de Myologie
Marion Masingue - Assistance Publique – Hôpitaux de Paris
Diane Giovannini - Centre Hospitalier Universitaire de Grenoble
Martin B Delatycki - Murdoch Children's Research Institute
Elsdon Storey - The Alfred Hospital
Mac Gardner - University of Otago
David J Amor - Murdoch Children's Research Institute
Garth Nicholson - Anzac Research Institute
Steve Vucic - The University of Sydney
Robert D Henderson - Royal Brisbane and Women's Hospital
Thomas Robertson - Royal Brisbane and Women's Hospital
Jason Dyke - Royal Perth Hospital
Vicki Fabian - Royal Perth Hospital
Frank Mastaglia - Perron Institute for Neurological and Translational Science
Mark R Davis - Pathwest Laboratory Medicine
Marina Kennerson - Anzac Research Institute
Ros Quinlivan - Dubowitz Neuromuscular Centre, UCL Great Ormond Street Institute of Child Health & MRC Centre for Neuromuscular Diseases, London, United Kingdom
Simon Hammans - University Hospital Southampton NHS Foundation Trust
Arianna Tucci - Queen Mary University of London
Melanie Bahlo - The University of Melbourne
Catriona A McLean - The University of Melbourne
Nigel G Laing - The University of Western Australia
Tanya Stojkovic - Assistance Publique – Hôpitaux de Paris
Henry Houlden - University College London
Michael G Hanna - National Hospital for Neurology and Neurosurgery
Ira W Deveson - Garvan Institute of Medical Research
Paul J Lockhart - Royal Children's Hospital
Phillipa J Lamont - Royal Perth Hospital
Michael C Fahey - Monash Children’s Hospital
Enrico Bugiardini - National Hospital for Neurology and Neurosurgery
Gianina Ravenscroft - The University of Western Australia
OPDM study group
Stephan L Zuchner - Leadership Department
Publication Details: Nature communications, Vol.15(1), pp.6327-15
Grant note: Wellcome Trust MR/T001712/1 / RCUK | Medical Research Council (MRC)
Academic Unit: Leadership Department; Miller School of Medicine; John P. Hussman Institute for Human Genomics
Language: English
Resource Type: Journal article
PMID: 39068203
Record Identifier: 991032795975302976