title: Dystrophin hydrophobic regions in the pathogenesis of Duchenne and Becker muscular dystrophies.
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.
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province. liangyingyin@hotmail.com.
authors.forename: Yingyin
authors.initials: Y
authors.lastname: Liang
authors.forename: Songlin
authors.initials: S
authors.lastname: Chen
authors.forename: Jianzong
authors.initials: J
authors.lastname: Zhu
authors.forename: Xiangxue
authors.initials: X
authors.lastname: Zhou
authors.forename: Chen
authors.initials: C
authors.lastname: Yang
authors.forename: Lu
authors.initials: L
authors.lastname: Yao
authors.forename: Cheng
authors.initials: C
authors.lastname: Zhang
mesh_terms: D016189:Dystrophin / Q000737:chemistry* / Q000235:genetics*; D005838:Genotype; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D021621:Imaging, Three-Dimensional; D008968:Molecular Conformation; D020388:Muscular Dystrophy, Duchenne / Q000235:genetics*; D010641:Phenotype; D012189:Retrospective Studies; D017384:Sequence Deletion / Q000235:genetics*; D012984:Software
chemical_list: D016189:Dystrophin