TY - JOUR
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 - Wicklund, Matthew
N1 - Publisher Copyright:
© The Author(s) 2024.
PY - 2024/12
Y1 - 2024/12
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.
UR - https://www.scopus.com/pages/publications/85199806195
UR - https://www.scopus.com/pages/publications/85199806195#tab=citedBy
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
IS - 1
M1 - 6327
ER -