LGMD2I presenting with a characteristic Duchenne or Becker muscular dystrophy phenotype

Schwartz, Marianne; Hertz, Jens Michael; Sveen, Marie-Louise; Vissing, John

doi:10.1212/01.wnl.0000157654.59374.e5

Cited by 65 publications

(57 citation statements)

References 10 publications

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“…Similar to that observed in the skeletal muscles, dystrophin expression improved further with the increase in doses. A measure of (1)(2)(3)(4)(5)(6), heart tissues (7-11) and cadiomyocytes (12)(13)(14). 1, sample from control TA muscle; 12, freshly isolated cardiomyocytes without treatment; 2, 3, 7, 8 and 13, 2 days after 50 mg ml -1 morpholinoE23 treatment; 4, 5, 9, 10 and 14, 5 days after the treatment; 6 and 11, 7days after the treatment.…”

Section: Higher Doses Of Morpholinoe23 Induced Dystrophin Expression mentioning

confidence: 99%

“…1 In-frame mutations in the dystrophin gene also cause a milder form of Becker muscular dystrophy with expression of truncated but partially functional dystrophin proteins. [2][3][4] The amount of dystrophin in Becker muscular dystrophy varies, but can reach 30% or higher of normal levels, in contrast to only a few revertant fibers in the majority of DMD. 5 The DMD gene consists of 79 exons spanning 42.3 million base pairs.…”

Section: Introductionmentioning

confidence: 99%

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Dose-dependent restoration of dystrophin expression in cardiac muscle of dystrophic mice by systemically delivered morpholino

et al. 2009

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We have earlier shown that antisense morpholino oligomers are able to restore dystrophin expression by systemic delivery in body-wide skeletal muscles of dystrophic mdx mice. However, the levels of dystrophin expression vary considerably and, more importantly, no dystrophin expression has been achieved in cardiac muscle. In this study, we investigate the efficiency of morpholino-induced exon skipping in cardiomyoblasts and myocytes in vitro, and in cardiac muscle in vivo by dose escalation. We showed that morpholino induces targeted exon skipping equally effectively in both skeletal muscle myoblasts and cardiomyoblasts. Effective exon skipping was achieved in cardiomyocytes in culture. In the mdx mice, morpholino rescues dystrophin expression dose dependently in both skeletal and cardiac muscles. Therapeutic levels of dystrophin were achieved in cardiac muscle albeit at higher doses than in skeletal muscles. Up to 50 and 30% normal levels of dystrophin were induced by single systemic delivery of 3 g kg -1 of morpholino in skeletal and cardiac muscles, respectively. High doses of morpholino treatment reduced the serum levels of creatine kinase without clear toxicity. These findings suggest that effective rescue of dystrophin in cardiac muscles can be achieved by morpholino for the treatment of Duchenne muscular dystrophy.

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Section: Higher Doses Of Morpholinoe23 Induced Dystrophin Expression mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Dose-dependent restoration of dystrophin expression in cardiac muscle of dystrophic mice by systemically delivered morpholino

et al. 2009

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“…Limb girdle muscular dystrophy (LGMD) is a differential diagnosis to BMD and DMD. By re-screening patients with an initial diagnosis of DMD and BMD, but without verified DMD mutations, we previously identified 11 patients with mutations in the gene for fukutin-related protein (LGMD type 2I) (Schwartz et al, 2005). Such a diagnostic mistake could have serious consequences for prognostic and genetic counselling.…”

Section: Discussionmentioning

confidence: 99%

Deletion of exon 16 of the dystrophin gene is not associated with disease

et al. 2007

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The DNA of a male harbored a deletion of exon 16 as well as most of introns 15 and 16 of the dystrophin gene. The person was completely healthy, with universal normal muscle strength, and normal muscle histology and creatine kinase levels. The deletion was also present in DNA from a muscle biopsy, excluding mosaicism as an explanation for the phenotype. We conclude that the protein segment encoded by exon 16 of the dystrophin gene is of no importance for the essential function of dystrophin. The findings suggest that even large gene re-arrangements of the dystrophin gene may not always be disease-causing, and caution a diagnosis of dystrophinopathy in sporadic cases of single exon in-frame deletions.

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“…Diseases to consider when making a differential diagnosis include limb-girdle muscular dystrophies [32], EmeryDreifuss muscular dystrophy and dilated cardiomyopathy [33].…”

Section: Diagnostic Settingmentioning

confidence: 99%