Low-level dystrophin expression attenuating the dystrophinopathy phenotype

Neuromuscular Disorders

Volumn 28, Issue 2, 2018, Pages 116-121

  Waldrop, Megan A ^a,b   Gumienny, Felecia ^a   El Husayni, Saleh ^c   Frank, Diane E ^c   Weiss, Robert B ^d   Flanigan, Kevin M ^a,b  

^a NATIONWIDE CHILDREN S HOSPITAL   (United States)

^b OHIO STATE UNIVERSITY   (United States)

^c AVI BIOPHARMA INC   (United States)

^d UNIVERSITY OF UTAH SCHOOL OF MEDICINE   (United States)

Author keywords

Dystrophin; Intermediate muscular dystrophy; Nonsense mutation; RNA sequencing

Indexed keywords

DYSTROPHIN; DMD PROTEIN, HUMAN;

ARTICLE; CASE REPORT; CHILD; CLINICAL ARTICLE; DUCHENNE MUSCULAR DYSTROPHY; DYSTROPHINOPATHY; EXON SKIPPING; GENE; GENETIC TRANSCRIPTION; HAPLOTYPE; HOMOZYGOSITY; HUMAN; IMMUNOBLOTTING; LTBP4 GENE; MALE; MUSCLE BIOPSY; NONSENSE MUTATION; PRIORITY JOURNAL; PROTEIN EXPRESSION; RNA SEQUENCE; SCHOOL CHILD; SIX MINUTE WALK TEST; EXON; GENE EXPRESSION; GENETICS; METABOLISM; PATHOLOGY; PHENOTYPE; SKELETAL MUSCLE; STOP CODON;

CHILD; CODON, NONSENSE; DYSTROPHIN; EXONS; GENE EXPRESSION; HUMANS; MALE; MUSCLE, SKELETAL; MUSCULAR DYSTROPHY, DUCHENNE; PHENOTYPE;

EID: 85039842582     PISSN: 09608966     EISSN: 18732364     Source Type: Journal    
DOI: 10.1016/j.nmd.2017.11.007     Document Type: Article

References (28)

1. Flanigan, K.M., Duchenne and Becker muscular dystrophies. Neurol Clin 32 (2014), 671–688 viii.
2. Aartsma-Rus, A., Van Deutekom, J.C., Fokkema, I.F., Van Ommen, G.J., Den Dunnen, J.T., 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 34 (2006), 135–144.
3. Monaco, A.P., Bertelson, C.J., Liechti-Gallati, S., Moser, H., Kunkel, L.M., An explanation for the phenotypic differences between patients bearing partial deletions of the DMD locus. Genomics 2 (1988), 90–95.
4. Dent, K.M., Dunn, D.M., von Niederhausern, A.C., Aoyagi, A.T., Kerr, L., Bromberg, M.B., et al. Improved molecular diagnosis of dystrophinopathies in an unselected clinical cohort. Am J Med Genet A 134 (2005), 295–298.
5. Shiga, N., Takeshima, Y., Sakamoto, H., Inoue, K., Yokota, Y., Yokoyama, M., et al. Disruption of the splicing enhancer sequence within exon 27 of the dystrophin gene by a nonsense mutation induces partial skipping of the exon and is responsible for Becker muscular dystrophy. J Clin Invest 100 (1997), 2204–2210.
6. Tuffery-Giraud, S., Saquet, C., Thorel, D., Disset, A., Rivier, F., Malcolm, S., et al. Mutation spectrum leading to an attenuated phenotype in dystrophinopathies. Eur J Hum Genet 13 (2005), 1254–1260.
7. Flanigan, K.M., Dunn, D.M., von Niederhausern, A., Soltanzadeh, P., Howard, M.T., Sampson, J.B., et al. Nonsense mutation-associated Becker muscular dystrophy: interplay between exon definition and splicing regulatory elements within the DMD gene. Hum Mutat 32 (2011), 299–308.
8. Trabelsi, M., Beugnet, C., Deburgrave, N., Commere, V., Orhant, L., Leturcq, F., et al. When a mid-intronic variation of DMD gene creates an ESE site. Neuromuscul Disord 24 (2014), 1111–1117.
9. Banihani, R., Baskin, B., Halliday, W., Kobayashi, J., Kawamura, A., McAdam, L., et al. A novel mutation in DMD (c.10797+5G>A) causes Becker muscular dystrophy associated with intellectual disability. J Dev Behav Pediatr 37 (2016), 239–244.
10. Ginjaar, I.B., Kneppers, A.L., v d Meulen, J.D., Anderson, L.V., Bremmer-Bout, M., van Deutekom, J.C., et al. Dystrophin nonsense mutation induces different levels of exon 29 skipping and leads to variable phenotypes within one BMD family. Eur J Hum Genet 8 (2000), 793–796.
11. Melis, M.A., Muntoni, F., Cau, M., Loi, D., Puddu, A., Boccone, L., et al. Novel nonsense mutation (C→A nt 10512) in exon 72 of dystrophin gene leading to exon skipping in a patient with a mild dystrophinopathy. Hum Mutat(Suppl. 1), 1998, S137–S138.
12. Bouge, A.L., Murauer, E., Beyne, E., Miro, J., Varilh, J., Taulan, M., et al. Targeted RNA-Seq profiling of splicing pattern in the DMD gene: exons are mostly constitutively spliced in human skeletal muscle. Sci Rep, 7, 2017, 39094.
13. Goemans, N., Klingels, K., van den Hauwe, M., Boons, S., Verstraete, L., Peeters, C., et al. Six-minute walk test: reference values and prediction equation in healthy boys aged 5 to 12 years. PLoS ONE, 8, 2013 e84120.
14. Goemans, N., van den Hauwe, M., Wilson, R., van Impe, A., Klingels, K., Buyse, G., Ambulatory capacity and disease progression as measured by the 6-minute-walk-distance in Duchenne muscular dystrophy subjects on daily corticosteroids. Neuromuscul Disord 23 (2013), 618–623.
15. Flanigan, K.M., Ceco, E., Lamar, K.M., Kaminoh, Y., Dunn, D.M., Mendell, J.R., et al. LTBP4 genotype predicts age of ambulatory loss in Duchenne muscular dystrophy. Ann Neurol 73 (2013), 481–488.
16. Flanigan, K.M., Dunn, D.M., von Niederhausern, A., Soltanzadeh, P., Gappmaier, E., Howard, M.T., et al. Mutational spectrum of DMD mutations in dystrophinopathy patients: application of modern diagnostic techniques to a large cohort. Hum Mutat 30 (2009), 1657–1666.
17. Disset, A., Bourgeois, C.F., Benmalek, N., Claustres, M., Stevenin, J., Tuffery-Giraud, S., An exon skipping-associated nonsense mutation in the dystrophin gene uncovers a complex interplay between multiple antagonistic splicing elements. Hum Mol Genet 15 (2006), 999–1013.
18. Flanigan, K.M., Dunn, D., Larsen, C.A., Medne, L., Bonnemann, C.B., Weiss, R.B., Becker muscular dystrophy due to an inversion of exons 23 and 24 of the DMD gene. Muscle Nerve 44 (2011), 822–825.
19. Martone, J., Briganti, F., Legnini, I., Morlando, M., Picillo, E., Sthandier, O., et al. The lack of the Celf2a splicing factor converts a Duchenne genotype into a Becker phenotype. Nat Commun, 7, 2016, 10488.
20. Tuffery-Giraud, S., Chambert, S., Demaille, J., Claustres, M., Point mutations in the dystrophin gene: evidence for frequent use of cryptic splice sites as a result of splicing defects. Hum Mutat 14 (1999), 359–368.
21. Juan-Mateu, J., Gonzalez-Quereda, L., Rodriguez, M.J., Verdura, E., Lazaro, K., Jou, C., et al. Interplay between DMD point mutations and splicing signals in Dystrophinopathy phenotypes. PLoS ONE, 8, 2013 e59916.
22. Niba, E.T.E., Nishida, A., Tran, V.K., Vu, D.C., Matsumoto, M., Awano, H., et al. Cryptic splice activation but not exon skipping is observed in minigene assays of dystrophin c.9361+1G>A mutation identified by NGS. J Hum Genet 62 (2017), 531–537.
23. Deburgrave, N., Daoud, F., Llense, S., Barbot, J.C., Recan, D., Peccate, C., et al. Protein- and mRNA-based phenotype-genotype correlations in DMD/BMD with point mutations and molecular basis for BMD with nonsense and frameshift mutations in the DMD gene. Hum Mutat 28 (2007), 183–195.
24. Bello, L., Kesari, A., Gordish-Dressman, H., Cnaan, A., Morgenroth, L.P., Punetha, J., et al. Genetic modifiers of ambulation in the Cooperative International Neuromuscular Research Group Duchenne Natural History Study. Ann Neurol 77 (2015), 684–696.
25. van den Bergen, J.C., Hiller, M., Bohringer, S., Vijfhuizen, L., Ginjaar, H.B., Chaouch, A., et al. Validation of genetic modifiers for Duchenne muscular dystrophy: a multicentre study assessing SPP1 and LTBP4 variants. J Neurol Neurosurg Psychiatry 86 (2015), 1060–1065.
26. Mendell, J.R., Rodino-Klapac, L.R., Sahenk, Z., Roush, K., Bird, L., Lowes, L.P., et al. Eteplirsen for the treatment of Duchenne muscular dystrophy. Ann Neurol 74 (2013), 637–647.
27. Finkel, R.S., Flanigan, K.M., Wong, B., Bonnemann, C., Sampson, J., Sweeney, H.L., et al. Phase 2a study of ataluren-mediated dystrophin production in patients with nonsense mutation Duchenne muscular dystrophy. PLoS ONE, 8, 2013 e81302.
28. Bushby, K., Finkel, R., Wong, B., Barohn, R., Campbell, C., Comi, G.P., et al. Ataluren treatment of patients with nonsense mutation dystrophinopathy. Muscle Nerve 50 (2014), 477–487.