{Reference Type}: Case Reports
{Title}: Large in-frame 5' deletions in DMD associated with mild Duchenne muscular dystrophy: Two case reports and a review of the literature.
{Author}: Gibbs EM;Barthélémy F;Douine ED;Hardiman NC;Shieh PB;Khanlou N;Crosbie RH;Nelson SF;Miceli MC;
{Journal}: Neuromuscul Disord
{Volume}: 29
{Issue}: 11
{Year}: 11 2019
{Factor}: 3.538
{DOI}: 10.1016/j.nmd.2019.09.009
{Abstract}: Duchenne muscular dystrophy is caused by mutations in the dystrophin-encoding DMD gene. While Duchenne is most commonly caused by large intragenic deletions that cause frameshift and complete loss of dystrophin expression, in-frame deletions in DMD can result in the expression of internally truncated dystrophin proteins and may be associated with a milder phenotype. In this study, we describe two individuals with large in-frame 5' deletions (exon 3-23 and exon 3-28) that remove the majority of the N-terminal region, including part of the actin binding and central rod domains. Both patients had progressive muscle weakness during childhood but are observed to have a relatively mild disease course compared to typical Duchenne. We show that in muscle biopsies from both patients, truncated dystrophin is expressed at the sarcolemma. We have additionally developed a patient-specific fibroblast-derived cell model, which can be inducibly reprogrammed to form myotubes that largely recapitulate biopsy findings for the patient with the exon 3-23 deletion, providing a culture model for future investigation of this unusual case. We discuss these mutations in the context of previously reported 5' in-frame DMD deletions and relevant animal models, and review the spectrum of phenotypes associated with these deletions.