Deletion of dystrophin in-frame exon 5 leads to a severe phenotype: Guidance for exon skipping strategies

PLoS ONE

Volumn 11, Issue 1, 2016, Pages

  Toh, Zhi Yon Charles ^a,b   Aung Htut, May Thandar ^c   Pinniger, Gavin ^b   Adams, Abbie M ^a,b,c   Krishnaswarmy, Sudarsan ^b   Wong, Brenda L ^d   Fletcher, Sue ^a,b,c   Wilton, Steve D ^a,b,c  

^a Western Australian Research Inst   (Australia)

^b UNIVERSITY OF WESTERN AUSTRALIA   (Australia)

^c MURDOCH UNIVERSITY   (Australia)

^d CINCINNATI CHILDREN'S HOSPITAL MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DYSTROPHIN; ANTISENSE OLIGONUCLEOTIDE; RNA;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BECKER MUSCULAR DYSTROPHY; CHILD; CONTROLLED STUDY; DMD GENE; EXON SKIPPING; GENE; GENE DELETION; GENE DUPLICATION; GENE LOSS; GENE MAPPING; GENE MUTATION; GENE SEQUENCE; GENETIC CODE; HUMAN; HUMAN CELL; HUMAN TISSUE; IN VIVO STUDY; MALE; MOUSE; NONHUMAN; OPEN READING FRAME; PHENOTYPE; SCHOOL CHILD; ANIMAL; C57BL MOUSE; CELL CULTURE; CHEMISTRY; DISEASE MODEL; DUCHENNE MUSCULAR DYSTROPHY; EXON; GENETICS; METABOLISM; PATHOLOGY; RNA SPLICING; SEQUENCE ANALYSIS;

ANIMALS; CELLS, CULTURED; CHILD; DISEASE MODELS, ANIMAL; DYSTROPHIN; EXONS; HUMANS; MALE; MICE; MICE, INBRED C57BL; MUSCULAR DYSTROPHY, DUCHENNE; OLIGONUCLEOTIDES, ANTISENSE; PHENOTYPE; RNA; RNA SPLICING; SEQUENCE ANALYSIS, RNA; SEQUENCE DELETION;

EID: 84954341946     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0145620     Document Type: Article

References (44)

1. Worton RG, Thompson MW. Genetics of Duchenne muscular dystrophy. Annu Rev Genet. 1988; 22:601-29. Epub 1988/01/01. doi: 10.1146/annurev.ge.22.120188.003125 PMID: 3071259.
2. Muntoni F, Torelli S, Ferlini A. Dystrophin and mutations: one gene, several proteins, multiple phenotypes. Lancet Neurol. 2003; 2(12):731-40. Epub 2003/11/26. S1474442203005854 [pii]. PMID: 14636778.
3. Flanigan KM, von Niederhausern A, Dunn DM, Alder J, Mendell JR, Weiss RB. Rapid direct sequence analysis of the dystrophin gene. Am J Hum Genet. 2003; 72(4):931-9. PMID: 12632325.
4. Witting N, Duno M, Vissing J. Becker muscular dystrophy with widespread muscle hypertrophy and a non-sense mutation of exon 2. Neuromuscul Disord. 2012. Epub 2012/09/04. S0960-8966(12)00556-1 [pii] doi: 10.1016/j.nmd.2012.07.004 PMID: 22939275.
5. Dubowitz V. The Duchenne dystrophy story: from phenotype to gene and potential treatment. J Child Neurol. 1989; 4(4):240-50. PMID: 2677113.
6. Brooke MH, Fenichel GM, Griggs RC, Mendell JR, Moxley R, Miller JP, et al. Clinical investigation in Duchenne dystrophy: 2. Determination of the "power" of therapeutic trials based on the natural history. Muscle Nerve. 1983; 6(2):91-103. Epub 1983/02/01. doi: 10.1002/mus.880060204 PMID: 6343858.
7. Gangopadhyay SB, Sherratt TG, Heckmatt JZ, Dubowitz V, Miller G, Shokeir M, et al. Dystrophin in frameshift deletion patients with Becker muscular dystrophy. Am J Hum Genet. 1992; 51(3):562-70. Epub 1992/09/01. PMID: 1496988; PubMed Central PMCID: PMC1682710.
8. Malhotra SB, Hart KA, Klamut HJ, Thomas NS, Bodrug SE, Burghes AH, et al. Frame-shift deletions in patients with Duchenne and Becker muscular dystrophy. Science. 1988; 242(4879):755-9. PMID: 3055295.
9. Nevo Y, Muntoni F, Sewry C, Legum C, Kutai M, Harel S, et al. Large in-frame deletions of the rodshaped domain of the dystrophin gene resulting in severe phenotype. Isr Med Assoc J. 2003; 5(2):94-7. Epub 2003/04/05. PMID: 12674656.
10. Gualandi F, Rimessi P, Trabanelli C, Spitali P, Neri M, Patarnello T, et al. Intronic breakpoint definition and transcription analysis in DMD/BMD patients with deletion/duplication at the 5′ mutation hot spot of the dystrophin gene. Gene. 2006; 370:26-33. Epub 2006/01/28. S0378-1119(05)00698-0 [pii] doi: 10.1016/j.gene.2005.11.002 PMID: 16439068.
11. Wein N, Vulin A, Falzarano MS, Szigyarto CA, Maiti B, Findlay A, et al. Translation from a DMD exon 5 IRES results in a functional dystrophin isoform that attenuates dystrophinopathy in humans and mice. Nat Med. 2014; 20(9):992-1000. doi: 10.1038/nm.3628 PMID: 25108525; PubMed Central PMCID: PMC4165597.
12. Fletcher S, Adkin CF, Meloni P, Wong B, Muntoni F, Kole R, et al. Targeted exon skipping to address "leaky" mutations in the dystrophin gene. Mol Ther Nucleic Acids. 2012; 1:e48. Epub 2013/01/25. doi: 10.1038/mtna.2012.40 PMID: 23344648; PubMed Central PMCID: PMC3499695.
13. Gualandi F, Trabanelli C, Rimessi P, Calzolari E, Toffolatti L, Patarnello T, et al. Multiple exon skipping and RNA circularisation contribute to the severe phenotypic expression of exon 5 dystrophin deletion. J Med Genet. 2003; 40(8):e100. Epub 2003/08/16. PMID: 12920092.
14. Fragall CT, Adams AM, Johnsen RD, Kole R, Fletcher S, Wilton SD. Mismatched single stranded antisense oligonucleotides can induce efficient dystrophin splice switching. BMC Med Genet. 2011; 12:141. Epub 2011/10/22.1471-2350-12-141 [pii] doi: 10.1186/1471-2350-12-141 PMID: 22013876; PubMed Central PMCID: PMC3213239.
15. Mann CJ, Honeyman K, Cheng AJ, Ly T, Lloyd F, Fletcher S, et al. Antisense-induced exon skipping and synthesis of dystrophin in the mdx mouse. Proc Natl Acad Sci U S A. 2001; 98(1):42-7. PMID: 11120883.
16. Greer KL, Lochmuller H, Flanigan K, Fletcher S, Wilton SD. Targeted exon skipping to correct exon duplications in the dystrophin gene. Mol Ther Nucleic Acids. 2014; 3:e155. doi: 10.1038/mtna.2014.8 PMID: 24643206; PubMed Central PMCID: PMC3982197.
17. Beroud C, Tuffery-Giraud S, Matsuo M, Hamroun D, Humbertclaude V, Monnier N, et al. Multiexon skipping leading to an artificial DMD protein lacking amino acids from exons 45 through 55 could rescue up to 63% of patients with Duchenne muscular dystrophy. Hum Mutat. 2007; 28(2):196-202. PMID: 17041910.
18. Wilton SD, Veedu RN, Fletcher S. The emperor's new dystrophin: finding sense in the noise. Trends Mol Med. 2015; 21(7):417-26. doi: 10.1016/j.molmed.2015.04.006 PMID: 26051381.
19. Lattanzi L, Salvatori G, Coletta M, Sonnino C, Cusella De Angelis MG, Gioglio L, et al. 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. 1998; 101(10):2119-28. PMID: 9593768.
20. Harding PL, Fall AM, Honeyman K, Fletcher S, Wilton SD. The influence of antisense oligonucleotide length on dystrophin exon skipping. Mol Ther. 2007; 15(1):157-66. Epub 2006/12/14.6300006 [pii] doi: 10.1038/sj.mt.6300006 PMID: 17164787.
21. Wilton SD, Fall AM, Harding PL, McClorey G, Coleman C, Fletcher S. Antisense Oligonucleotide induced Exon Skipping Across the Human Dystrophin Gene Transcript. Mol Ther. 2007; 15(7):1288-96. PMID: 17285139.
22. Jearawiriyapaisarn N, Moulton HM, Buckley B, Roberts J, Sazani P, Fucharoen S, et al. Sustained Dystrophin Expression Induced by Peptide-conjugated Morpholino Oligomers in the Muscles of mdx Mice. Mol Ther. 2008; 16(9):1624-9. Epub 2008/06/12. mt2008120 [pii] doi: 10.1038/mt.2008.120 PMID: 18545222.
23. Roberts RG, Barby TF, Manners E, Bobrow M, Bentley DR. Direct detection of dystrophin gene rearrangements by analysis of dystrophin mRNA in peripheral blood lymphocytes. Am J Hum Genet. 1991; 49(2):298-310. PMID: 1867192.
24. Fletcher S, Honeyman K, Fall AM, Harding PL, Johnsen RD, Steinhaus JP, et al. Morpholino Oligomer-Mediated Exon Skipping Averts the Onset of Dystrophic Pathology in the mdx Mouse. Mol Ther. 2007; 15(9):1587-92. PMID: 17579573.
25. Moulton HM, Fletcher S, Neuman BW, McClorey G, Stein DA, Abes S, et al. Cell-penetrating peptidemorpholino conjugates alter pre-mRNA splicing of DMD (Duchenne muscular dystrophy) and inhibit murine coronavirus replication in vivo. Biochem Soc Trans. 2007; 35(Pt 4):826-8. PMID: 17635157.
26. Cooper ST, Lo HP, North KN. Single section Western blot: improving the molecular diagnosis of the muscular dystrophies. Neurology. 2003; 61(1):93-7. Epub 2003/07/09. PMID: 12847163.
27. Puchtler H, Waldrop FS, Valentine LS. Polarization microscopic studies of connective tissue stained with picro-sirius red FBA. Beitrage zur Pathologie. 1973; 150(2):174-87. PMID: 4129194.
28. Takeshima Y, Yagi M, Okizuka Y, Awano H, Zhang Z, Yamauchi Y, et al. Mutation spectrum of the dystrophin gene in 442 Duchenne/Becker muscular dystrophy cases from one Japanese referral center. J Hum Genet. 2010; 55(6):379-88. doi: 10.1038/jhg.2010.49 PMID: 20485447.
29. Winnard AV, Klein CJ, Coovert DD, Prior T, Papp A, Snyder P, et al. Characterization of translational frame exception patients in Duchenne/Becker muscular dystrophy. Hum Mol Genet. 1993; 2(6):737-44. Epub 1993/06/01. PMID: 8353493.
30. Tuffery-Giraud S, Beroud C, Leturcq F, Yaou RB, Hamroun D, Michel-Calemard L, et al. Genotype-phenotype analysis in 2,405 patients with a dystrophinopathy using the UMD-DMD database: a model of nationwide knowledgebase. Hum Mutat. 2009; 30(6):934-45. Epub 2009/04/16. doi: 10.1002/humu. 20976 PMID: 19367636.
31. Aartsma-Rus A, Van Deutekom JC, Fokkema IF, Van Ommen GJ, Den Dunnen JT. Entries in the Leiden Duchenne muscular dystrophy mutation database: an overview of mutation types and paradoxical cases that confirm the reading-frame rule. Muscle Nerve. 2006; 34(2):135-44. PMID: 16770791.
32. Magri F, Govoni A, D'Angelo MG, Del Bo R, Ghezzi S, Sandra G, et al. Genotype and phenotype characterization in a large dystrophinopathic cohort with extended follow-up. J Neurol. 2011. Epub 2011/03/15. doi: 10.1007/s00415-011-5979-z PMID: 21399986.
33. Gurvich OL, Maiti B, Weiss RB, Aggarwal G, Howard MT, Flanigan KM. DMD exon 1 truncating point mutations: amelioration of phenotype by alternative translation initiation in exon 6. Hum Mutat. 2009; 30 (4):633-40. Epub 2009/02/12. doi: 10.1002/humu.20913 PMID: 19206170; PubMed Central PMCID: PMC2663021.
34. Magri F, Del Bo R, D'Angelo MG, Govoni A, Ghezzi S, Gandossini S, et al. Clinical and molecular characterization of a cohort of patients with novel nucleotide alterations of the Dystrophin gene detected by direct sequencing. BMC medical genetics. 2011; 12:37. Epub 2011/03/15. doi: 10.1186/1471-2350-12-37. PMID: 21396098; PubMed Central PMCID: PMC3061890.
35. Flanigan KM, Dunn DM, von Niederhausern A, Soltanzadeh P, Howard MT, Sampson JB, et al. Nonsense mutation-associated Becker muscular dystrophy: interplay between exon definition and splicing regulatory elements within the DMD gene. Human mutation. 2011; 32(3):299-308. Epub 2011/10/06. doi: 10.1002/humu.21426 PMID: 21972111.
36. Greer K, Mizzi K, Rice E, Kuster L, Barrero RA, Bellgard MI, et al. Pseudoexon activation increases phenotype severity in a Becker muscular dystrophy patient. Mol Genet Genomic Med. 2015; 3(4):320-6. doi: 10.1002/mgg3.144 PMID: 26247048; PubMed Central PMCID: PMCPMC4521967.
37. Norwood FL, Sutherland-Smith AJ, Keep NH, Kendrick-Jones J. The structure of the N-terminal actinbinding domain of human dystrophin and how mutations in this domain may cause Duchenne or Becker muscular dystrophy. Structure. 2000; 8(5):481-91. PMID: 10801490.
38. Heald A, Anderson LV, Bushby KM, Shaw PJ. Becker muscular dystrophy with onset after 60 years. Neurology. 1994; 44(12):2388-90. PMID: 7991131.
39. Amann KJ, Renley BA, Ervasti JM. A cluster of basic repeats in the dystrophin rod domain binds F-actin through an electrostatic interaction. J Biol Chem. 1998; 273(43):28419-23. PMID: 9774469.
40. Ervasti JM, Rybakova IN, Amann KJ. A multiple site, side binding model for the interaction of dystrophin with F-actin. Soc Gen Physiol Ser. 1997; 52:31-44. PMID: 9210218.
41. Rybakova IN, Amann KJ, Ervasti JM. A new model for the interaction of dystrophin with F-actin. J Cell Biol. 1996; 135(3):661-72. PMID: 8909541; PubMed Central PMCID: PMC2121071.
42. McNaughton JC, Broom JE, Hill DF, Jones WA, Marshall CJ, Renwick NM, et al. A cluster of transposon-like repetitive sequences in intron 7 of the human dystrophin gene. J Mol Biol. 1993; 232(1):314-21. doi: 10.1006/jmbi.1993.1389 PMID: 8392588.
43. Matsumura K, Imoto N. [Two long-living brothers of dystrophin-related muscular dystrophy with an inframe deletion of exon 3 of the dystrophin gene-clinical features and diagnosis]. Rinsho Shinkeigaku. 1991; 31(3):286-90. PMID: 1893667.
44. Futamura N, Kawamoto K, Takahashi K, Funakawa I, Jinnai K. [Four siblings with becker muscular dystrophy (BMD) manifesting severe mental retardation]. Rinsho Shinkeigaku. 2006; 46(1):62-5. PMID: 16541798.