Study on Duchenne muscular dystrophy gene mutation and prenatal diagnosis / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To explore the characteristics of DNA mutations underlying Duchenne muscular dystrophy and provide prenatal diagnosis.</p><p><b>METHODS</b>Multiplex ligation-dependent probe amplification (MLPA) and denaturing high performance liquid chromatography (DHPLC) were applied for analyzing DMD gene mutations in 388 unrelated Chinese patients and 53 fetuses.</p><p><b>RESULTS</b>Respectively, 230 and 43 subjects were found to harbor a deletion (59.28%) or duplication (11.08%). Two deletion hotspots were identified, which have located at exons 45-54 and exons 3-19. Duplications were mainly detected at exons 2-43. Point mutations were identified in 29.64% of patients. Fifty three fetuses were prenatal diagnosed, among which 18 were identified as patients.</p><p><b>CONCLUSION</b>Frequencies of DMD gene deletions and duplications in China are similar to global data. Prenatal diagnosis can help to reduce births of DMD patients.</p>

Correlation between genotypes and phenotypes in pseudohypertrophic muscular dystrophy / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To explore the correlation between genotypes and phenotypes in Chinese patients with pseudohypertrophic muscular dystrophy.</p><p><b>METHODS</b>Patients with Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) were diagnosed clinically. Multiplex ligation-dependent probe amplification (MLPA) were performed to detect potential DMD gene mutations. The results were analyzed statistically.</p><p><b>RESULTS</b>Among 280 patients, 238(85.0%) were diagnosed with DMD, 35(12.50%) were diagnosed with BMD and 7(2.5%) were diagnosed with intermediate muscular dystrophin (IMD). Among these, 252(92.31%) were in-frame mutations, and 21(7.69%) were out-of-frame mutations. Twelve patients with DMD have carried in-frame mutations, 9 with BMD have carried frame-shift mutations, and 7 IMD patients have carried frame-shift mutation.</p><p><b>CONCLUSION</b>Most of the genotypes and phenotypes of DMD have complied with the reading-frame hypothesis. Patients with BMD with frame-shift mutations may facilitate understanding of the pathogenesis of DMD, and provide a theoretical basis for clinical therapy.</p>

Clinical, electromyographic and cervical magnetic resonance imaging features of Hirayama disease / 中华神经医学杂志

Objective To investigate the clinical, electromyographic and cervical magnetic resonance imaging (MRI) characteristics of Hirayama disease. Methods Fifteen patients with Hirayama disease were observed for special clinical manifestations and underwent electromyographic examination of the bilateral distal upper limb muscles and peripheral nerve conduction velocity. MRI of the neck in neutral and fully flexed positions was performed to identify potential lower cervical cord atrophy and cervical curvature anomalies. Results All the 15 male patients had disease onset during puberty with asymmetric muscular atrophy and weakness of the hands and forearms. Concentric needle electromyography revealed prolonged duration and large amplitude of the motor unit potentials in the compromised distal limb muscles with also increased polyphasic potentials and poor recruitment, involving mainly the C7, C8 and T1 myotomes. In neutral neck position, MRI identified lower cervical cord atrophy in 9 patients, occurring mainly at C5, C6 levels;in fully flexed position, all patients showed forward displacement and flattening of the lower cervical cord, occurring mostly at C6 level. Conclusion Hirayama disease occurs mainly in puberty in young male patients, whose clinical features and electromyographic examination often indicate localized anterior horn anomalies in the lower cervical cord. MRI of the neck in neutral and fully flexed position can provide valuable assistance in the diagnosis of this disease.

Preliminary study of the spatial structural and functional changes of dystrophin after exon-3 deletion / 南方医科大学学报

<p><b>OBJECTIVE</b>To explore the structural and functional changes of dystrophin molecule after exon 3 deletion.</p><p><b>METHODS</b>Three-dimensional models of dystrophin comprising the major domains were established before and after exon 3 deletion using SWISS-MODEL server. The motifs and structural domains of dystrophin after exon 3 deletion were searched in Pfam database, and the crystal structure of the actin-binding domain in the dystrophin molecule was analyzed using Rasmol software.</p><p><b>RESULTS</b>Torsion of the N-terminal actin-binding domain occurred in the dystrophin molecule after deletion of exon 3. Homology analysis based on Pfam database searches indicated that following exon 3 deletion, the Bit score of the first calponin homology (CH1) domain was decreased from 108 to 36.5 while its expectation value increased from 2.3e-9 to 8.1e-8. The deletion also resulted in the absence of the spiral region C from the CH1 domain.</p><p><b>CONCLUSION</b>Exon 3 deletion in the dystrophin-coding sequence decreases the stability of CH1 domain and prevents the formation of the junction interface where dystrophin binds to actin. The bioinformatics approach provides a new alternative for investigation of the pathogenesis of DMD pathogenesy investigation.</p>

Identification of disease-causing mutations in DMD gene of Duchenne muscular dystrophy / 中华神经医学杂志

Objective To detect the disease-causing mutations in Duchenne muscular dystrophy (DMD) gene of DMD or Becher's muscular dystrophy (BMD) patients or carriers. Methods Multiplex ligation-dependent probe amplification (MLPA) and denaturing high performance liquid chromatography (DHPLC) were coupled to analyze the disease-causing mutations in DMD gene. Results Ten patients were detected to have deletions in different exons; 1 patient was caused by duplication of exon 50 using DHPLC analysis, and 4 patients were found to be caused by non-sense point mutations. However, the disease-causing mutations of other 5 patients remained to be determined. Conclusion MLPA coupled with DHPLC analysis can be used to detect the disease-causing mutations of DMD or BMD systematically, and provide valuable information for the affected families in preventing from recurrence of DMD or BMD.