Becker muscular dystrophy due to an intronic splicing mutation inducing a dual dystrophin transcript.
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.
Center for Neuromuscular Diseases and Neuropathies, Unit of Neurology, ASST "Spedali Civili", University of Brescia, Brescia, Italy.
Alice
A
Todeschini
Department of Medical Sciences, Logistic Unit of Medical Genetics, University- Hospital of Ferrara, Italy.
Francesca
F
Gualandi
Department of Medical Sciences, Logistic Unit of Medical Genetics, University- Hospital of Ferrara, Italy.
Cecilia
C
Trabanelli
Department of Medical Sciences, Logistic Unit of Medical Genetics, University- Hospital of Ferrara, Italy.
Annarita
A
Armaroli
Department of Medical Sciences, Logistic Unit of Medical Genetics, University- Hospital of Ferrara, Italy.
Anna
A
Ravani
Department of Neurosciences, University of Padua, Padua.
Marina
M
Fanin
Center for Neuromuscular Diseases and Neuropathies, Unit of Neurology, ASST "Spedali Civili", University of Brescia, Brescia, Italy.
Silvia
S
Rota
Department of Neurosciences, University of Padua, Padua.
Luca
L
Bello
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.
Alessandra
A
Ferlini
Department of Neurosciences, University of Padua, Padua.
Elena
E
Pegoraro
Center for Neuromuscular Diseases and Neuropathies, Unit of Neurology, ASST "Spedali Civili", University of Brescia, Brescia, Italy.
Alessandro
A
Padovani
Center for Neuromuscular Diseases and Neuropathies, Unit of Neurology, ASST "Spedali Civili", University of Brescia, Brescia, Italy. Electronic address: massimiliano.filosto@unibs.it.
Massimiliano
M
Filosto
D000328:Adult; D016189:Dystrophin / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007438:Introns; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D020388:Muscular Dystrophy, Duchenne / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D010641:Phenotype; D020033:Protein Isoforms
C484258:DMD protein, human; D016189:Dystrophin; D020033:Protein Isoforms
Becker muscular dystrophy; Duchenne muscular dystrophy; Dystrophin; Dystrophin amount; Dystrophinopathy; Splicing mutation