Characterization of undiagnosed Austrian LGMD patients

Limb Girdle Muscular Dystrophies (LGMD) are a group of rare muscle diseases that cause progressive weakness in the muscles around the hips and shoulders. These diseases can severely impact quality of life of affected patients, leading to a high disease burden. Although modern genetic testing has improved diagnosis, many people with LGMD still do not get a clear answer, leaving them without a confirmed diagnosis or direction for treatment. In a recent study of Austrian patients with LGMD, several individuals were found to carry genetic changes called "variants of uncertain significance". These are changes in genes that might be linked to muscle disease, but their exact effect is not yet known. Because these genetic changes affect proteins important for muscle and nerve function, we believe they deserve further investigation. Our project aims to understand how these uncertain gene changes affect muscle cells and contribute to disease. To do this, we will use a variety of methods, including lab-based experiments, analysis of patient muscle samples, and advanced models using human stem cells and mice. Our goals are to determine how these gene changes affect the body at the cellular level, whether they are truly harmful, and if there are ways to correct their effects. We believe that this research will not only help provide clear diagnoses for the patients involved, but also improve our overall understanding of LGMD. Ultimately, our work will lead to better patient care, improved diagnostic tools, and new directions for treatmentnot just for LGMD, but potentially for other rare muscle diseases as well.