Uncovering the true features of dystrophin gene rearrangement and improving the molecular diagnosis of Duchenne and Becker muscular dystrophies.

Duchenne and Becker muscular dystrophies (DMD/BMD) are caused by complex mutations in the dystrophin gene (DMD). Currently, there is no integrative method for the precise detection of all potential DMD variants, a gap which we aimed to address using long-read sequencing. The captured long-read sequencing panel developed in this study was applied to 129 subjects, including 11 who had previously unsolved cases. The results showed that this method accurately detected DMD mutations, ranging from single-nucleotide variations to structural variations. Furthermore, our findings revealed that continuous exon duplication/deletion in the DMD/BMD cohort may be attributed to complex segmental rearrangements and that noncontiguous duplication/deletion is generally attributed to intragenic inversion or interchromosome translocation. Mutations in the deep introns were confirmed to produce a pseudoexon. Moreover, variations in female carriers were precisely identified. The integrated and precise DMD gene screening method proposed in this study could improve the molecular diagnosis of DMD/BMD.

Spectroscopic study on the interaction of Aß42 with di(picolyl)amine derivatives and the toxicity to SH-S5Y5 cells.

In order to confirm the neurotoxicity of bifunctional chelators containing hydrophobic groups and metal chelating moiety, the interaction of di(picolyl)amine (dpa) derivatives toward Aß42 peptide was investigated. Fluorescence titration reveals that a hydrophobic chelator (such as BODIPY) shows high binding affinity to amyloid Aß42. Circular dichroism (CD) spectra confirm that the hydrophobic bifunctional chelator can decrease α-helix fraction and increase the ß-sheet fraction of amyloid Aß42. In particular, experimental results indicate that a bifunctional chelator can assemble with Cu(II)-Aß42 forming chelator-Cu(II)-Aß42 nanospheres, which are toxic to SH-S5Y5 cells. The hydrophobic interaction between the chelator and the amyloid peptide (Aß42) has great contribution to the formation of neurotoxic chelator-Cu(II)-Aß42 nanospheres. This work gives a general guide to the development of low cytotoxic inhibitors of Aß42 aggregation.