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

Cortese, A; HANNA, MG; Beecroft, SJ; Facchini, S; Curro, R; Cabrera-Serrano, M; Stevanovski, I; Chintalaphani, SR; Gamaarachchi, H; Weisburd, B; Folland, C; Monahan, G; Scriba, CK; Dofash, L; Johari, M; Grosz, BR; Ellis, M; Fearnley, LG; Tankard, R; Read, J; Merve, A; Dominik, N; Vegezzi, E; Schnekenberg, RP; Fernandez-Eulate, G; Masingue, M; Giovannini, D; Delatycki, MB; Storey, E; Gardner, M; Amor, DJ; Nicholson, G; Vucic, S; Henderson, RD; Robertson, T; Dyke, J; Fabian, V; Mastaglia, F; Davis, MR; Kennerson, M; Quinlivan, R; Hammans, S; Tucci, A; Bahlo, M; McLean, CA; Laing, NG; Stojkovic, T; Houlden, H; Deveson, IW; Lockhart, PJ; Lamont, PJ; Fahey, MC; Bugiardini, E; Ravenscroft, G

Author(s): Cortese, A; HANNA, MG; Beecroft, SJ; Facchini, S; Curro, R; Cabrera-Serrano, M; Stevanovski, I; Chintalaphani, SR; Gamaarachchi, H; Weisburd, B; Folland, C; Monahan, G; Scriba, CK; Dofash, L; Johari, M; Grosz, BR; Ellis, M; Fearnley, LG; Tankard, R; Read, J; Merve, A; Dominik, N; Vegezzi, E; Schnekenberg, RP; Fernandez-Eulate, G; Masingue, M; Giovannini, D; Delatycki, MB; Storey, E; Gardner, M; Amor, DJ; Nicholson, G; Vucic, S; Henderson, RD; Robertson, T; Dyke, J; Fabian, V; Mastaglia, F; Davis, MR; Kennerson, M; Quinlivan, R; Hammans, S; Tucci, A; Bahlo, M; McLean, CA; Laing, NG; Stojkovic, T; Houlden, H; Deveson, IW; Lockhart, PJ; Lamont, PJ; Fahey, MC; Bugiardini, E; Ravenscroft, G;
Details: Publication Year 2024-07-27,Volume 15,Issue #1,Page 6327
Journal Title: Nature Communications
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.
Publisher: Springer Nature
Keywords: Humans; Male; Female; Adult; *Trinucleotide Repeat Expansion/genetics; Middle Aged; *White People/genetics; *Muscle, Skeletal/pathology; ATP-Binding Cassette Transporters/genetics; Myopathies, Structural, Congenital/genetics/pathology; Pedigree; Aged; Young Adult; Fibroblasts/metabolism/pathology; Muscle Weakness/genetics/pathology; Adolescent; Muscular Dystrophies
Research Division(s): Population Health And Immunity
PubMed ID: 39068203
Publisher's Version: https://doi.org/10.1038/s41467-024-49950-2
Open Access at Publisher's Site: https://doi.org/10.1038/s41467-024-49950-2
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2024-07-31 03:30:15

Last Modified: 2024-10-25 10:50:49