Pseudoexon activation increases phenotype severity in a becker muscular dystrophy patient

Molecular Genetics and Genomic Medicine

Volumn 3, Issue 4, 2015, Pages 320-326

  Greer, Kane ^a,b   Mizzi, Kayla ^b   Rice, Emily ^b   Kuster, Lukas ^b   Barrero, Roberto A ^a   Bellgard, Matthew I ^a   Lynch, Bryan J ^c   Foley, Aileen Reghan ^c   Rathallaigh, Eoin O ^d   Wilton, Steve D ^a,b,e   Fletcher, Sue ^a,b,e  

^a MURDOCH UNIVERSITY   (Australia)

^b UNIVERSITY OF WESTERN AUSTRALIA   (Australia)

^c CHILDREN S UNIVERSITY HOSPITAL   (Ireland)

^d Central Remedial Clinic Ireland   (Ireland)

^e Western Australian Biomedical Research Institute   (Australia)

Author keywords

Cryptic splicing; Duchenne Becker muscular dystrophy; Dystrophin; Exon splicing enhancer; Pseudoexon

Indexed keywords

EID: 84954321783     PISSN: None     EISSN: 23249269     Source Type: Journal    
DOI: 10.1002/mgg3.144     Document Type: Article

References (25)

1. Arechavala-Gomeza, V., K. Anthony, J. Morgan, and F. Muntoni. 2012. Antisense oligonucleotide-mediated exon skipping for Duchenne muscular dystrophy: progress and challenges. Curr. Gene Ther. 12:152–160.
2. Beggs, A. H., E. P. Hoffman, J. R. Snyder, K. Arahata, L. Specht, F. Shapiro, et al. 1991. Exploring the molecular basis for variability among patients with Becker muscular dystrophy: dystrophin gene and protein studies. Am. J. Hum. Genet. 49:54–67.
3. van den Bergen, J. C., B. H. Wokke, A. A. Janson, S. G. van Duinen, M. A. Hulsker, H. B. Ginjaar, et al. 2014. Dystrophin levels and clinical severity in Becker muscular dystrophy patients. J. Neurol. Neurosurg. Psychiatry 85:747–753.
4. Bushby, K. M., D. Gardner-Medwin, L. V. Nicholson, M. A. Johnson, I. D. Haggerty, N. J. Cleghorn, et al. 1993. The clinical, genetic and dystrophin characteristics of Becker muscular dystrophy. II. Correlation of phenotype with genetic and protein abnormalities. J. Neurol. 240:105–112.
5. Bushby, K., R. Finkel, D. J. Birnkrant, L. E. Case, P. R. Clemens, L. Cripe, et al. 2010. Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and pharmacological and psychosocial management. Lancet Neurol. 9:77–93.
6. Cirak, S., V. Arechavala-Gomeza, M. Guglieri, L. Feng, S. Torelli, K. Anthony, et al. 2011. Exon skipping and dystrophin restoration in patients with Duchenne muscular dystrophy after systemic phosphorodiamidate morpholino oligomer treatment: an open-label, phase 2, dose-escalation study. Lancet 378:595–605.
7. Cohn, R. D., and K. P. Campbell. 2000. Molecular basis of muscular dystrophies. Muscle Nerve 23:1456–1471.
8. Dastur, R. S., P. S. Gaitonde, S. V. Khadilkar, and J. J. Nadkarni. 2008. Becker muscular dystrophy in Indian patients: analysis of dystrophin gene deletion patterns. Neurol. India 56:374–378.
9. Den Dunnen, J. T., P. M. Grootscholten, E. Bakker, L. A. Blonden, H. B. Ginjaar, M. C. Wapenaar, et al. 1989. Topography of the Duchenne muscular dystrophy (DMD) gene: FIGE and cDNA analysis of 194 cases reveals 115 deletions and 13 duplications. Am. J. Hum. Genet. 45:835–847.
10. Desmet, F. O., D. Hamroun, M. Lalande, G. Collod-Beroud, M. Claustres, and C. Beroud. 2009. Human Splicing Finder: an online bioinformatics tool to predict splicing signals. Nucleic Acids Res. 37:e67.
11. Ferlini, A., N. Galie, L. Merlini, C. Sewry, A. Branzi, and F. Muntoni. 1998. A novel Alu-like element rearranged in the dystrophin gene causes a splicing mutation in a family with X-linked dilated cardiomyopathy. Am. J. Hum. Genet. 63:436–446.
12. Fletcher, S., P. L. Meloni, R. D. Johnsen, B. L. Wong, F. Muntoni, and S. D. Wilton. 2013. Antisense suppression of donor splice site mutations in the dystrophin gene transcript. Mol. Genet. Genomic Med. 1:162–173.
13. Guglieri, M., and K. Bushby. 2010. Molecular treatments in Duchenne muscular dystrophy. Curr. Opin. Pharmacol. 10:331–337.
14. Kesari, A., L. N. Pirra, L. Bremadesam, O. McIntyre, E. Gordon, A. L. Dubrovsky, et al. 2008. Integrated DNA, cDNA, and protein studies in Becker muscular dystrophy show high exception to the reading frame rule. Hum. Mutat. 29:728–737.
15. Lattanzi, L., G. Salvatori, M. Coletta, C. Sonnino, M. G. Cusella De Angelis, L. Gioglio, et al. 1998. High efficiency myogenic conversion of human fibroblasts by adenoviral vector-mediated MyoD gene transfer. An alternative strategy for ex vivo gene therapy of primary myopathies. J. Clin. Invest. 101:2119–2128.
16. Malik, V., L. R. Rodino-Klapac, L. Viollet, C. Wall, W. King, R. Al-Dahhak, et al. 2010. Gentamicin-induced readthrough of stop codons in Duchenne muscular dystrophy. Ann. Neurol. 67:771–780.
17. Mendell, J. R., L. R. Rodino-Klapac, Z. Sahenk, K. Roush, L. Bird, L. P. Lowes, et al. 2013. Eteplirsen for the treatment of Duchenne muscular dystrophy. Ann. Neurol. 74:637–647.
18. Monaco, A. P., C. J. Bertelson, S. Liechti-Gallati, H. Moser, and L. M. Kunkel. 1988. An explanation for the phenotypic differences between patients bearing partial deletions of the DMD locus. Genomics 2:90–95.
19. Muntoni, F., S. Torelli, and A. Ferlini. 2003. Dystrophin and mutations: one gene, several proteins, multiple phenotypes. Lancet Neurol. 2:731–740.
20. Rodino-Klapac, L. R., J. R. Mendell, and Z. Sahenk. 2013. Update on the treatment of Duchenne muscular dystrophy. Curr. Neurol. Neurosci. Rep. 13:332.
21. Sironi, M., R. Cagliani, U. Pozzoli, A. Bardoni, G. P. Comi, R. Giorda, et al. 2002. The dystrophin gene is alternatively spliced throughout its coding sequence. FEBS Lett. 517:163–166.
22. Sironi, M., R. Cagliani, G. P. Comi, U. Pozzoli, A. Bardoni, R. Giorda, et al. 2003. Trans-acting factors may cause dystrophin splicing misregulation in BMD skeletal muscles. FEBS Lett. 537:30–34.
23. Wilton, S. D., and S. Fletcher. 2011. RNA splicing manipulation: strategies to modify gene expression for a variety of therapeutic outcomes. Curr. Gene Ther. 11:259–275.
24. Wilton, S. D., A. M. Fall, P. L. Harding, G. McClorey, C. Coleman, and S. Fletcher. 2007. Antisense oligonucleotide-induced exon skipping across the human dystrophin gene transcript. Mol. Ther. 15:1288–1296.
25. Winnard, A. V., C. J. Klein, D. D. Coovert, T. Prior, A. Papp, P. Snyder, et al. 1993. Characterization of translational frame exception patients in Duchenne/Becker muscular dystrophy. Hum. Mol. Genet. 2:737–744.