Lab Med Online.  2015 Jul;5(3):121-126. 10.3343/lmo.2015.5.3.121.

Novel Non-contiguous Duplications in the DMD Gene in Five Patients with Duchenne Muscular Dystrophy

Affiliations
  • 1Department of Laboratory Medicine, Yonsei University College of Medicine, Seoul, Korea. KAL1119@yuhs.ac
  • 2Department of Rehabilitation, Institute of Neuromuscular Disease, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.

Abstract

BACKGROUND
Muscular dystrophy is an X-linked recessive disorder caused by mutations in the DMD gene. Muscular dystrophy is classified into 2 types; Duchenne muscular dystrophy (DMD), which has severe clinical symptoms, and Becker muscular dystrophy (BMD), which has much milder clinical symptoms. Phenotypic progression to either DMD or BMD can be predicted by analyzing mutations in DMD by using the reading frame rule.
METHODS
Of 88 patients with mutations in DMD, which were detected using Multiplex Ligation-dependent Probe Amplification DMD test kit (MRC-Holland, The Netherlands), medical records of 5 patients with non-contiguous duplications were reviewed. These rare non-contiguous duplications in DMD were compared with those reported previously.
RESULTS
We identified 3 novel non-contiguous duplications in DMD that included exons 2-7 and 45-51, exons 5-37 and 50-59, and exons 52-53 and 56-61. The 5 patients with these non-contiguous duplications showed the phenotypic features of DMD. Especially, duplication of exons 52-53 and 56-61 was observed in a family, i.e., 2 DMD-affected brothers and their carrier mother.
CONCLUSIONS
Prediction of phenotypes associated with complex non-contiguous duplications by using the reading frame rule is difficult because the duplications affect the expression of DMD together. Because most patients with non-contiguous duplications showed the phenotypic features of DMD, the reading frame rule should be interpreted cautiously. This study provides important insights on the non-contiguous duplications in DMD for understanding genotype-phenotype correlations and for developing dystrophin for therapeutic purpose
s.

Keyword

Duchenne muscular dystrophy; DMD gene; Non-contiguous duplication; Multiplex ligation-dependent probe amplification (MLPA)
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