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

OPDM study group; Andrea Cortese; Macarena Cabrera-Serrano; Chiara Folland; Gavin Monahan; Carolin K. Scriba; Lein Dofash; Mridul Johari; Frank Mastaglia; Nigel G. Laing; Gianina Ravenscroft

doi:10.1038/s41467-024-49950-2

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

OPDM study group, Andrea Cortese, Macarena Cabrera-Serrano, Chiara Folland, Gavin Monahan, Carolin K. Scriba, Lein Dofash, Mridul Johari, Frank Mastaglia, Nigel G. Laing, Gianina Ravenscroft

Research output: Contribution to journal › Article › peer-review

4 Citations (Scopus)

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.

Original language	English
Article number	6327
Number of pages	15
Journal	Nature Communications
Volume	15
DOIs	https://doi.org/10.1038/s41467-024-49950-2
Publication status	Published - 27 Jul 2024

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10.1038/s41467-024-49950-2Licence: CC BY

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@article{f61518b5dfdc456b96e4df5ea9d7fbfe,

title = "A CCG expansion in ABCD3 causes oculopharyngodistal myopathy in individuals of European ancestry",

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.",

author = "{OPDM study group} and Andrea Cortese and Beecroft, {Sarah J.} and Stefano Facchini and Riccardo Curro and Macarena Cabrera-Serrano and Igor Stevanovski and Chintalaphani, {Sanjog R.} and Hasindu Gamaarachchi and Ben Weisburd and Chiara Folland and Gavin Monahan and Scriba, {Carolin K.} and Lein Dofash and Mridul Johari and Grosz, {Bianca R.} and Melina Ellis and Fearnley, {Liam G.} and Rick Tankard and Justin Read and Ashirwad Merve and Natalia Dominik and Elisa Vegezzi and Schnekenberg, {Ricardo P.} and Gorka Fernandez-Eulate and Marion Masingue and Diane Giovannini and Delatycki, {Martin B.} and Elsdon Storey and Mac Gardner and Amor, {David J.} and Garth Nicholson and Steve Vucic and Henderson, {Robert D.} and Thomas Robertson and Jason Dyke and Vicki Fabian and Frank Mastaglia and Davis, {Mark R.} and Marina Kennerson and Ros Quinlivan and Simon Hammans and Arianna Tucci and Melanie Bahlo and McLean, {Catriona A.} and Laing, {Nigel G.} and Tanya Stojkovic and Henry Houlden and Hanna, {Michael G.} and Deveson, {Ira W.} and Lockhart, {Paul J.} and Lamont, {Phillipa J.} and Fahey, {Michael C.} and Enrico Bugiardini and Gianina Ravenscroft and Piraye Oflazer and Ba{\c s}ak, {Nazli A.} and H{\"u}lya Kayserili and G{\"o}zde Ye{\c s}il and Edoardo Malfatti and Lilliker, {James B.} and Matthew Wicklund and Pitceathly, {Robert D.S.} and Stefen Brady and Bernard Brais and David Pellerin and Stephan Zuchner and Danzi, {Matt C.} and Marina Grandis and Comi, {Giacomo P.} and Corti, {Stefania P.} and Elena Abati and Antonio Toscano and Arianna Manini and Arianna Ghia and Cristina Tassorelli and Ilaria Quartesan and Roberto Simone and Rossor, {Alexander M.} and Reilly, {Mary M.} and Liam Carroll and Volker Straub and Bjarne Udd and Zhiyong Chen and Gis{\`e}le Bonne",

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doi = "10.1038/s41467-024-49950-2",

language = "English",

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T1 - A CCG expansion in ABCD3 causes oculopharyngodistal myopathy in individuals of European ancestry

AU - OPDM study group

AU - Cortese, Andrea

AU - Beecroft, Sarah J.

AU - Facchini, Stefano

AU - Curro, Riccardo

AU - Cabrera-Serrano, Macarena

AU - Stevanovski, Igor

AU - Chintalaphani, Sanjog R.

AU - Gamaarachchi, Hasindu

AU - Weisburd, Ben

AU - Folland, Chiara

AU - Monahan, Gavin

AU - Scriba, Carolin K.

AU - Dofash, Lein

AU - Johari, Mridul

AU - Grosz, Bianca R.

AU - Ellis, Melina

AU - Fearnley, Liam G.

AU - Tankard, Rick

AU - Read, Justin

AU - Merve, Ashirwad

AU - Dominik, Natalia

AU - Vegezzi, Elisa

AU - Schnekenberg, Ricardo P.

AU - Fernandez-Eulate, Gorka

AU - Masingue, Marion

AU - Giovannini, Diane

AU - Delatycki, Martin B.

AU - Storey, Elsdon

AU - Gardner, Mac

AU - Amor, David J.

AU - Nicholson, Garth

AU - Vucic, Steve

AU - Henderson, Robert D.

AU - Robertson, Thomas

AU - Dyke, Jason

AU - Fabian, Vicki

AU - Mastaglia, Frank

AU - Davis, Mark R.

AU - Kennerson, Marina

AU - Quinlivan, Ros

AU - Hammans, Simon

AU - Tucci, Arianna

AU - Bahlo, Melanie

AU - McLean, Catriona A.

AU - Laing, Nigel G.

AU - Stojkovic, Tanya

AU - Houlden, Henry

AU - Hanna, Michael G.

AU - Deveson, Ira W.

AU - Lockhart, Paul J.

AU - Lamont, Phillipa J.

AU - Fahey, Michael C.

AU - Bugiardini, Enrico

AU - Ravenscroft, Gianina

AU - Oflazer, Piraye

AU - Başak, Nazli A.

AU - Kayserili, Hülya

AU - Yeşil, Gözde

AU - Malfatti, Edoardo

AU - Lilliker, James B.

AU - Wicklund, Matthew

AU - Pitceathly, Robert D.S.

AU - Brady, Stefen

AU - Brais, Bernard

AU - Pellerin, David

AU - Zuchner, Stephan

AU - Danzi, Matt C.

AU - Grandis, Marina

AU - Comi, Giacomo P.

AU - Corti, Stefania P.

AU - Abati, Elena

AU - Toscano, Antonio

AU - Manini, Arianna

AU - Ghia, Arianna

AU - Tassorelli, Cristina

AU - Quartesan, Ilaria

AU - Simone, Roberto

AU - Rossor, Alexander M.

AU - Reilly, Mary M.

AU - Carroll, Liam

AU - Straub, Volker

AU - Udd, Bjarne

AU - Chen, Zhiyong

AU - Bonne, Gisèle

PY - 2024/7/27

Y1 - 2024/7/27

N2 - 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.

AB - 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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U2 - 10.1038/s41467-024-49950-2

DO - 10.1038/s41467-024-49950-2

M3 - Article

C2 - 39068203

AN - SCOPUS:85199806195

SN - 2041-1723

VL - 15

JO - Nature Communications

JF - Nature Communications

M1 - 6327

ER -

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

Abstract

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Novel genomic approaches to identify the missing genetics underlying skeletal muscle disease

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

Abstract

Access to Document

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Novel genomic approaches to identify the missing genetics underlying skeletal muscle disease

Cite this