1. A CCG expansion in ABCD3 causes oculopharyngodistal myopathy in individuals of European ancestry.
- Author
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Cortese A, 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, Hanna MG, Deveson IW, Lockhart PJ, Lamont PJ, Fahey MC, Bugiardini E, and Ravenscroft G
- Subjects
- Humans, Male, Female, Adult, Middle Aged, ATP-Binding Cassette Transporters genetics, Myopathies, Structural, Congenital genetics, Myopathies, Structural, Congenital pathology, Pedigree, Aged, Young Adult, Fibroblasts metabolism, Fibroblasts pathology, Muscle Weakness genetics, Muscle Weakness pathology, Adolescent, Muscular Dystrophies, Trinucleotide Repeat Expansion genetics, White People genetics, Muscle, Skeletal pathology
- 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., (© 2024. The Author(s).)
- Published
- 2024
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