Journal of Genetic Medicine

Korean Society of Medical Genetics and Genomics (대한의학유전학회)
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Identification of two novel Duchenne muscular dystrophies mutations in patients with Becker muscular dystrophy

  • Kim, Dahye (Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine) ;
  • Kim, Yoon-Myung (Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine) ;
  • Seo, Go Hun (Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine) ;
  • Kim, Gu Hwan (Medical Genetics Center, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine) ;
  • Yoo, Han Wook (Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine) ;
  • Yum, Mi-Sun (Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine) ;
  • Ko, Tae-Sung (Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine) ;
  • Lee, Beom Hee (Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine)
  • Received : 2017.07.17
  • Accepted : 2017.10.13
  • Published : 2017.12.31
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Abstract

Duchenne and Becker muscular dystrophies (DMD and BMD, respectively) are X-linked neuromuscular disorders characterized by progressive muscle weakness and severe skeletal muscle degeneration. BMD is a milder form with a later onset. Patients with BMD tend to survive much longer than those with DMD. The differentiation between DMD and BMD is important in the genetic counseling of affected patients and their families. Since muscle biopsies are invasive procedures, the differential diagnosis of BMD and DMD is often dependent on the mutation identified in the DMD gene in affected patients. However, when a novel DMD mutation is identified, the differential diagnosis should be based on muscle biopsy findings with other clinical findings. Here we describe two Korean patients with BMD confirmed by muscle biopsy and genetic testing. Two novel exonic deletions in the DMD gene were identified.

Keywords

References

  1. Mah JK, Korngut L, Dykeman J, Day L, Pringsheim T, Jette N. A systematic review and meta-analysis on the epidemiology of Duchenne and Becker muscular dystrophy. Neuromuscul Disord 2014;24:482-91. https://doi.org/10.1016/j.nmd.2014.03.008
  2. Bushby K, Finkel R, Birnkrant DJ, Case LE, Clemens PR, Cripe L, et al. Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and pharmacological and psychosocial management. Lancet Neurol 2010;9:77-93. https://doi.org/10.1016/S1474-4422(09)70271-6
  3. Bushby KM, Gardner-Medwin D, Nicholson LV, Johnson MA, Haggerty ID, Cleghorn NJ, et al. The clinical, genetic and dystrophin characteristics of Becker muscular dystrophy. II. Correlation of phenotype with genetic and protein abnormalities. J Neurol 1993;240:105-12. https://doi.org/10.1007/BF00858726
  4. Hoffman EP, Fischbeck KH, Brown RH, Johnson M, Medori R, Loike JD, et al. Characterization of dystrophin in muscle-biopsy specimens from patients with Duchenne's or Becker's muscular dystrophy. N Engl J Med 1988;318:1363-8. https://doi.org/10.1056/NEJM198805263182104
  5. Nicholson LV, Johnson MA, Bushby KM, Gardner-Medwin D, Curtis A, Ginjaar IB, et al. Integrated study of 100 patients with Xp21 linked muscular dystrophy using clinical, genetic, immunochemical, and histopathological data. Part 3. Differential diagnosis and prognosis. J Med Genet 1993;30:745-51. https://doi.org/10.1136/jmg.30.9.745
  6. Bushby KM. Genetic and clinical correlations of Xp21 muscular dystrophy. J Inherit Metab Dis 1992;15:551-64. https://doi.org/10.1007/BF01799614
  7. Banihani R, Smile S, Yoon G, Dupuis A, Mosleh M, Snider A, et al. Cognitive and neurobehavioral profile in boys with Duchenne muscular dystrophy. J Child Neurol 2015;30:1472-82. https://doi.org/10.1177/0883073815570154
  8. 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;55:379-88. https://doi.org/10.1038/jhg.2010.49
  9. Yazaki M, Yoshida K, Nakamura A, Koyama J, Nanba T, Ohori N, et al. Clinical characteristics of aged Becker muscular dystrophy patients with onset after 30 years. Eur Neurol 1999;42:145-9. https://doi.org/10.1159/000008089
  10. Nicolas A, Raguenes-Nicol C, Ben Yaou R, Ameziane-Le Hir S, Cheron A, Vie V, et al. Becker muscular dystrophy severity is linked to the structure of dystrophin. Hum Mol Genet 2015;24:1267-79. https://doi.org/10.1093/hmg/ddu537
  11. Anthony K, Cirak S, Torelli S, Tasca G, Feng L, Arechavala-Gomeza V, et al. Dystrophin quantification and clinical correlations in Becker muscular dystrophy: implications for clinical trials. Brain 2011;134:3547-59. https://doi.org/10.1093/brain/awr291
  12. van den Bergen JC, Wokke BH, Janson AA, van Duinen SG, Hulsker MA, Ginjaar HB, et al. Dystrophin levels and clinical severity in Becker muscular dystrophy patients. J Neurol Neurosurg Psychiatry 2014;85:747-53. https://doi.org/10.1136/jnnp-2013-306350
  13. Neri M, Torelli S, Brown S, Ugo I, Sabatelli P, Merlini L, et al. Dystrophin levels as low as 30% are sufficient to avoid muscular dystrophy in the human. Neuromuscul Disord 2007;17:913-8. https://doi.org/10.1016/j.nmd.2007.07.005
  14. Yang J, Li SY, Li YQ, Cao JQ, Feng SW, Wang YY, et al. MLPA-based genotype-phenotype analysis in 1053 Chinese patients with DMD/BMD. BMC Med Genet 2013;14:29.
  15. Barzegar M, Habibi P, Bonyady M, Topchizadeh V, Shiva S. Exon deletion pattern in duchene muscular dystrophy in north west of Iran. Iran J Child Neurol 2015;9:42-8.
  16. Cirak S, Arechavala-Gomeza V, Guglieri M, Feng L, Torelli S, Anthony K, et al. 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 2011;378:595-605. https://doi.org/10.1016/S0140-6736(11)60756-3