AI Article Synopsis

  • Dystrophinopathies are neuromuscular disorders caused by changes in the DMD gene and are passed down through X-linked recessive inheritance.
  • Advances in technology like next generation sequencing can detect about 99% of these genetic variants, but some cases require deeper analysis, such as mRNA studies from muscle biopsies.
  • In a reported case, a child suspected of Duchenne muscular dystrophy had a muscle biopsy indicating dystrophin deficiency despite negative genetic tests; mRNA analysis uncovered a pseudoexon activation due to a novel genetic variant, illustrating the importance of this method in challenging cases.

Article Abstract

Dystrophinopathies are a group of neuromuscular disorders, inherited in an X-linked recessive manner, caused by pathogenic variants in the DMD gene. Copy number variation detection and next generation sequencing allow the detection of around 99 % of the pathogenic variants. However, some patients require mRNA studies from muscle biopsies to identify deep intronic pathogenic variants. Here, we report a child suspected of having Duchenne muscular dystrophy, with a muscle biopsy showing dystrophin deficiency, and negative molecular testing for deletions, duplications, and small variants. mRNA analysis from muscle biopsy revealed a pseudoexon activation that introduce a premature stop codon into the reading frame. gDNA sequencing allowed to identified a novel variant, c.832-186 T>G, which creates a cryptic donor splice site, recognizing the underlying mechanism causing the pseudoexon insertion. This case highlights the usefulness of the mRNA analysis from muscle biopsy when routine genetic testing is negative and clinical suspicion of dystrophinopathies remains the main clinical diagnosis suspicion.

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Source
http://dx.doi.org/10.1016/j.gene.2024.148862DOI Listing

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