A Deletion in Duchenne Muscular Dystrophy Gene Found Through Whole Exome Sequencing in Iran.

Duchenne muscular dystrophy (DMD) is a severe progressive X-linked neuromuscular illness that affects movement through mutations in dystrophin gene. The mutation leads to insufficient, lack of, or dysfunction of dystrophin. The cause of DMD was determined in an Iranian family. Exome sequencing was carried out along with a complete physical examination of the family. In silico methods were applied to find the alteration in the protein structure. The homozygous variant in DMD gene (NM-004006.2) was defined as c.2732-2733delTT (p.Phe911CysfsX8) in exon 21. In addition, phylogenetic conservation study of the human dystrophin protein sequence revealed that phenylalanine 911 is one of the evolutionarily conserved amino acids. In conclusion, our study indicated a new deletion in the DMD gene in the affected family. This deletion with an X-linked inheritance pattern is new in Iran. These findings could facilitate genetic counseling for this family and other patients in the future.

Neuroprotective effect of L-deprenyl on the expression level of the Mst1 gene and inhibition of apoptosis in rat-model spinal cord injury.

Objectives: After primary tissue damage as a result of spinal cord injury (SCI), there is a period of secondary damage, which includes several cellular and inflammatory biochemical cascades. As a novel pro-apoptotic kinase, Mst1 (serine/threonine kinase 4) promotes programmed cell death in an inflammatory disease model. This study aimed to evaluate Mst1 gene expression levels in rats with spinal cord injury treated with L- deprenyl. Materials and Methods: The rats were divided into control (contusion), laminectomy, sham-operated (contused rats received 1 ml normal saline intraperitoneal), and treatment (contused rats received 5 mg/kg of L-deprenyl intraperitoneal; once a day for 7 days). The BBB (Basso, Beattie, and Bresnahan) scales were performed to assess motor function following SCI. Rats were sacrificed 28 days after SCI and the spinal cord lesion area was removed. Apoptosis and cavity formation in the spinal cord were determined by H&E staining and TUNEL assay, respectively. The mRNA levels of the Mst1, Nrf2, Bcl-2, and PGC1 α genes were analyzed using real-time quantitative PCR. Results: The results showed significant improvement in motor function in the L- deprenyl group compared with the untreated group. Histological analysis showed a significant reduction in the number of tunnel-positive cells after injection of L-deprenyl, as well as a decrease in the volume of the cavity. In addition, L-deprenyl treatment increased the expression of the Nrf2, Bcl-2, and PGC1 α genes, while reducing the expression of the Mst1 gene in the spinal nerves. Conclusion: These results suggest that L-deprenyl is a promising treatment for spinal cord injury.