Becker muscular dystrophy due to an intronic splicing mutation inducing a dual dystrophin transcript.

Autor: Todeschini A; Center for Neuromuscular Diseases and Neuropathies, Unit of Neurology, ASST 'Spedali Civili', University of Brescia, Brescia, Italy., Gualandi F; Department of Medical Sciences, Logistic Unit of Medical Genetics, University- Hospital of Ferrara, Italy., Trabanelli C; Department of Medical Sciences, Logistic Unit of Medical Genetics, University- Hospital of Ferrara, Italy., Armaroli A; Department of Medical Sciences, Logistic Unit of Medical Genetics, University- Hospital of Ferrara, Italy., Ravani A; Department of Medical Sciences, Logistic Unit of Medical Genetics, University- Hospital of Ferrara, Italy., Fanin M; Department of Neurosciences, University of Padua, Padua., Rota S; Center for Neuromuscular Diseases and Neuropathies, Unit of Neurology, ASST 'Spedali Civili', University of Brescia, Brescia, Italy., Bello L; Department of Neurosciences, University of Padua, Padua., Ferlini A; Department of Medical Sciences, Logistic Unit of Medical Genetics, University- Hospital of Ferrara, Italy; Dubowitz Neuromuscular Centre, Developmental Neuroscience Programme, UCL Institute of Child Health, London, UK., Pegoraro E; Department of Neurosciences, University of Padua, Padua., Padovani A; Center for Neuromuscular Diseases and Neuropathies, Unit of Neurology, ASST 'Spedali Civili', University of Brescia, Brescia, Italy., Filosto M; Center for Neuromuscular Diseases and Neuropathies, Unit of Neurology, ASST 'Spedali Civili', University of Brescia, Brescia, Italy. Electronic address: massimiliano.filosto@unibs.it.
Jazyk: angličtina
Zdroj: Neuromuscular disorders : NMD [Neuromuscul Disord] 2016 Oct; Vol. 26 (10), pp. 662-665. Date of Electronic Publication: 2016 Aug 16.
DOI: 10.1016/j.nmd.2016.08.007
Abstrakt: We describe a 29-year-old patient who complained of left thigh muscle weakness since he was 23 and of moderate proximal weakness of both lower limbs with difficulty in climbing stairs and running since he was 27. Mild weakness of iliopsoas and quadriceps muscles and muscle atrophy of both the distal forearm and thigh were observed upon clinical examination. He harboured a novel c.1150-3C>G substitution in the DMD gene, affecting the intron 10 acceptor splice site and causing exon 11 skipping and an out-of-frame transcript. However, protein of normal molecular weight but in reduced amounts was observed on Western Blot analysis. Reverse transcription analysis on muscle RNA showed production, via alternative splicing, of a transcript missing exon 11 as well as a low abundant full-length transcript which is enough to avoid the severe Duchenne phenotype. Our study showed that a reduced amount of full length dystrophin leads to a mild form of Becker muscular dystrophy. These results confirm earlier findings that low amounts of dystrophin can be associated with a milder phenotype, which is promising for therapies aiming at dystrophin restoration.
(Copyright © 2016 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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