A CCG expansion in ABCD3 causes oculopharyngodistal myopathy in individuals of European ancestry
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Published:2024-07-27
Issue:1
Volume:15
Page:
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ISSN:2041-1723
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Container-title:Nature Communications
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language:en
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Short-container-title:Nat Commun
Author:
Cortese AndreaORCID, Beecroft Sarah J.ORCID, Facchini Stefano, Curro Riccardo, Cabrera-Serrano MacarenaORCID, Stevanovski IgorORCID, Chintalaphani Sanjog R., Gamaarachchi Hasindu, Weisburd BenORCID, Folland Chiara, Monahan GavinORCID, Scriba Carolin K.ORCID, Dofash Lein, Johari Mridul, Grosz Bianca R.ORCID, Ellis Melina, Fearnley Liam G.ORCID, Tankard RickORCID, Read Justin, Merve Ashirwad, Dominik Natalia, Vegezzi Elisa, Schnekenberg Ricardo P., Fernandez-Eulate Gorka, Masingue Marion, Giovannini Diane, Delatycki Martin B., Storey Elsdon, Gardner Mac, Amor David J.ORCID, Nicholson GarthORCID, Vucic SteveORCID, Henderson Robert D., Robertson Thomas, Dyke JasonORCID, Fabian Vicki, Mastaglia Frank, Davis Mark R., Kennerson Marina, Oflazer Piraye, Başak Nazli A., Kayserili Hülya, Yeşil Gözde, Malfatti Edoardo, Lilliker James B., Wicklund Matthew, Pitceathly Robert D. S., Brady Stefen, Brais Bernard, Pellerin David, Zuchner Stephan, Danzi Matt C., Grandis Marina, Comi Giacomo P., Corti Stefania P., Abati Elena, Toscano Antonio, Manini Arianna, Ghia Arianna, Tassorelli Cristina, Quartesan Ilaria, Simone Roberto, Rossor Alexander M., Reilly Mary M., Carroll Liam, Straub Volker, Udd Bjarne, Chen Zhiyong, Bonne Gisèle, Quinlivan Ros, Hammans Simon, Tucci Arianna, Bahlo MelanieORCID, McLean Catriona A.ORCID, Laing Nigel G., Stojkovic Tanya, Houlden HenryORCID, Hanna Michael G., Deveson Ira W.ORCID, Lockhart Paul J.ORCID, Lamont Phillipa J., Fahey Michael C.ORCID, Bugiardini EnricoORCID, Ravenscroft GianinaORCID,
Abstract
AbstractOculopharyngodistal 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.
Funder
RCUK | Medical Research Council
Publisher
Springer Science and Business Media LLC
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