Dystrophin hydrophobic regions in the pathogenesis of Duchenne and Becker muscular dystrophies

  • Yingyin Liang Department of Neurology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province
  • Songlin Chen Department of Neurology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province
  • Jianzong Zhu Department of Neurology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province
  • Xiangxue Zhou Department of Neurology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province
  • Chen Yang Physical examination center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, China
  • Lu Yao Department of Neurology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province
  • Cheng Zhang Department of Neurology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province
Keywords: DMD, BMD, dystrophin, Kyte-Doolittle scale mean hydrophobicity profile, 3D model, genotype–phenotype analysis

Abstract

The aim of our study was to determine the role of dystrophin hydrophobic regions in the pathogenesis of Duchenne (DMD) and Becker (BMD) muscular dystrophies, by the Kyte-Doolittle scale mean hydrophobicity profile and 3D molecular models. A total of 1038 cases diagnosed with DMD or BMD with the in-frame mutation were collected in our hospital and the Leiden DMD information database in the period 2002-2013. Correlation between clinical types and genotypes were determined on the basis of these two sources. In addition, the Kyte-Doolittle scale mean hydrophobicity of dystrophin was analyzed using BioEdit software and the models of the hydrophobic domains of dystrophin were constructed. The presence of four hydrophobic regions is confirmed. They include the calponin homology CH2 domain on the actin-binding domain (ABD), spectrin-type repeat 16, hinge III and the EF Hand domain. The severe symptoms of DMD usually develop as a result of the mutational disruption in the hydrophobic regions I, II and IV of dystrophin – those that bind associated proteins of the dystrophin-glycoprotein complex (DGC). On the other hand, when the hydrophobic region III is deleted, the connection of the ordered repeat domains of the central rod domain remains intact, resulting in the less severe clinical presentation. We conclude that mutational changes in the structure of hydrophobic regions of dystrophin play an important role in the pathogenesis of DMD.

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Published
2015-05-20
How to Cite
1.
Liang Y, Chen S, Zhu J, Zhou X, Yang C, Yao L, Zhang C. Dystrophin hydrophobic regions in the pathogenesis of Duchenne and Becker muscular dystrophies. Bosn J of Basic Med Sci [Internet]. 2015May20 [cited 2019Nov.12];15(2):42-9. Available from: https://bjbms.org/ojs/index.php/bjbms/article/view/300
Section
Molecular Biology