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 V Monahan; Carolin K Scriba; Lein Dofash; Mridul Johari; Bianca R Grosz; Melina Ellis; Liam G Fearnley; Rick Tankard; Justin Read; Natalia Dominik; Ashirwad Merve; 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

doi:10.1038/s41467-024-49950-2

Back

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

Journal article

Open access

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), 6327

2024

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

PMID: 39068203

Files and links (1)

pdf

Published3.54 MBDownload View

Open Access CC BY V4.0

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.

Details

Title: A CCG expansion in ABCD3 causes oculopharyngodistal myopathy in individuals of European ancestry
Authors/Creators: Andrea Cortese
Sarah J Beecroft
Stefano Facchini
Riccardo Curro
Macarena Cabrera-Serrano
Igor Stevanovski
Sanjog R Chintalaphani
Hasindu Gamaarachchi
Ben Weisburd
Chiara Folland
Gavin V Monahan
Carolin K Scriba
Lein Dofash
Mridul Johari
Bianca R Grosz
Melina Ellis
Liam G Fearnley
Rick Tankard
Justin Read
Natalia Dominik
Ashirwad Merve
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
Publication Details: Nature communications, Vol.15(1), 6327
Publisher: Springer Nature
Grant note: Wellcome Trust MR/T001712/1 / RCUK | Medical Research Council (MRC)
Identifiers: 991005897388007891
Murdoch Affiliation: Research and Innovation Office
Language: English
Resource Type: Journal article

Metrics

1 Record Views

21 Times Cited - Web of Science