Manipulation of dystrophin pre-mRNA processing offers the potential to overcome mutations in the dystrophin gene that would otherwise lead to Duchenne muscular dystrophy.
It has been difficult to offer genetic counseling and prenatal diagnosis for Duchenne muscular dystrophy in the families of these isolated carriers, largely due to the difficulty in determining which of the dystrophin alleles segregating in the family harbors the mutation in the heterozygote.
Recently, Exondys51, a drug that aims to correct splicing defects in the dystrophin gene was approved by the US Food and Drug Administration (FDA) for the treatment of Duchenne muscular dystrophy (DMD).
Reprogramming of human Peripheral Blood Mononuclear Cell (PBMC) from a Chinese patient suffering Duchenne muscular dystrophy to iPSC line (SDQLCHi007-A) carrying deletion of 49-50 exons in the DMD gene.
DNA prepared from these hybrids was probed with sequences physically close to the locus; these include a junction fragment from the site of the X:21 translocation (pXJ1) and subclones from the pERT 87 (DXS164) region which are absent in a minority of male DMD patients.
When the PCR was used to amplify a region of the dystrophin gene encompassing exon 44 from genomic DNA of two Japanese brothers with DMD, it was found to be approximately 600 bp larger than expected.
In this study we aimed to detect mutations within the dystrophin gene in DMD patients, to determine the carrier status of women, and to perform a prenatal diagnosis.
Duchenne muscular dystrophy (DMD) is characterized by muscle degeneration and structural defects in the neuromuscular synapse that are caused by mutations in dystrophin.
Mutations of the dystrophin gene leading to a complete loss of the protein cause Duchenne muscular dystrophy (DMD), frequently associated with severe cardiomyopathy.
Seven patients with Duchenne muscular dystrophy with deletions in the open reading frame of DMD that are responsive to exon 51 skipping were selected on the basis of the preservation of their extensor digitorum brevis (EDB) muscle seen on MRI and the response of cultured fibroblasts from a skin biopsy to AVI-4658.
To investigate this, we examined the intracellular Ca2+ concentration and calcium transients in cardiomyocytes differentiated from human induced pluripotent stem cells (hiPSCs). hiPSCs were derived from a DMD patient (DMD-hiPSCs), in whom exon 44 of the gene encoding dystrophin was deleted, and from his parents (control-hiPSCs), who did not carry this mutation.
The field of inherited skeletal muscle disease research has advanced rapidly since the identification of mutations in the dystrophin gene as the cause of Duchenne muscular dystrophy in 1987.