Common therapeutic advances for Duchenne muscular dystrophy (DMD).

Background and purpose: Duchenne muscular dystrophy (DMD), a lethal X-linked recessive muscle dystrophy, is resulted in by different mutations including mostly frame-shifting gross deletions and duplications and rarely point mutations in DMD gene. Increasing weakness, progressive loss of skeletal muscle mass, and later-onset cardiomyopathy are serious clinical symptoms which ultimately lead to cardiac and respiratory failure, and premature death in DMD patients by age of 30. DMD is a prevalent genetic disorder and considers as an interesting target for gene therapy approaches. Massive gene size and existence of enormous number of muscle tissues are terrific hindrance against DMD treatments, nevertheless enormous efforts have been executed in the fields of gene replacement therapy, gene editing strategies, cell-based treatments, and small drug medications. Hot spot exons skipping and suppression of premature stop codons are the most interesting treatments for restoring functional DMD product, dystrophin protein. Clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein (Cas) systems are the most interesting genome editing platforms that are able to restore open reading frame of DMD gene. CRISPR-Cas9 and CRISPR-Cpf1 are two main genome editing sub-types that successfully used in mdx mice.Conclusions: This review aims to present recent progresses and future prospects over three main DMD therapeutic subgroups including gene therapy, cell therapy, and pharmacological therapy.

Whole Exome Sequencing to Find Candidate Variants for the Prediction of Kidney Transplantation Efficacy.

INTRODUCTION: Kidney transplantation is the optimal treatment strategy for some end-stage renal disease (ESRD); however, graft survival and the success of the transplantation depend on several elements, including the genetics of recipients. In this study, we evaluated exon loci variants based on a high-resolution Next Generation Sequencing (NGS) method. METHODS: We evaluated whole-exome sequencing (WES) of transplanted kidney recipients in a prospective study. The study involved a total of 10 patients (5 without a history of rejection and 5 with). About five milliliters of blood were collected for DNA extraction, followed by whole-exome sequencing based on molecular inversion probes (MIPs). RESULTS: Sequencing and variant filtering identified nine pathogenic variants in rejecting patients (low survival). Interestingly, in five patients with successful kidney transplantation, we found 86 SNPs in 63 genes 61 were variants of uncertain significance (VUS), 5 were likely pathogenic, and five were likely benign/benign. The only overlap between rejecting and non-rejecting patients was SNPs rs529922492 in rejecting and rs773542127 in non-rejecting patients' MUC4 gene. CONCLUSIONS: Nine variants of rs779232502, rs3831942, rs564955632, rs529922492, rs762675930, rs569593251, rs192347509, rs548514380, and rs72648913 have roles in short graft survival.