Inherited NMDs form a large group of diseases such as Limb-Girdle Muscular Dystrophies (LGMD), Congenital Muscular Dystrophies (CMD), Duchenne Muscular Dystrophy (DMD), Spinal Muscular Atrophy (SMA) and Charcot-Marie-Tooth disease (CMT). These pathologies are present in all human populations, affecting both sexes and children as well as adults. Approximately 1 in 3500 people will have a disabling inherited neuromuscular disease presenting in childhood or in later life. Within a given disease group (i.e. DMD, SMA), an enormous clinical heterogeneity is observed. The precise diagnosis of neuromuscular diseases requires both an extensive clinical examination and targeted complementary tests that include biological analyses, electromyography, imaging, and histological analysis of biopsies. Additionally, since many of the genes associated with these diseases are known, molecular and genetic tests are performed to confirm the diagnosis and discriminate through the identification of the precise genotype. However, a differential molecular assay is often required for each condition, which is highly complex, time consuming and expensive with the current state of the art molecular testing technologies. As a consequence, many patients remain without genetic confirmation of their disease: to date 30 to 40 % of LGMD patients have no genetic confirmation of their diagnosis. Importantly, new cutting edge therapies, such as exon skipping and nonsense skipping cannot be envisaged when no precise genetic diagnosis is available. New molecular diagnosis tools, enabling rapid, reliable and cost-effective comprehensive sequencing of numerous NMD genes are thus required. The development of such tools would allow accurate genetic diagnosis of NMDs patients, thus allowing them to benefit from cutting-edge therapies. Microarrays have the potential to address this issue, in a time and cost effective way. We propose to design a set of microarray-based tools that will enable the high- throughput comprehensive identification of genetic variants underlying inherited neuromuscular disorders (inherited NMDs) including Congenital Muscular Dystrophies (CMDs), Duchenne and Becker Muscular Dystrophy (DMD and BMD), Emery Dreifuss Muscular Dystrophy (EDMD), Limb-Girdle Muscular Dystrophies (LGMD), and Spinal Muscular Atrophy (SMA). This project will develop the technology and protocols leading to a novel highly sensitive, rapid and reliable diagnostic tool for enhanced molecular testing for inherited NMDs.
We propose to design a set of microarray-based tools that will enable the high- throughput comprehensive identification of genetic variants underlying inherited neuromuscular disorders (inherited NMDs) including Congenital Muscular Dystrophies (CMDs), Duchenne and Becker Muscular Dystrophy (DMD and BMD), Emery Dreifuss Muscular Dystrophy (EDMD), Limb-Girdle Muscular Dystrophies (LGMD), and Spinal Muscular Atrophy (SMA). This project will develop the technology and protocols leading to a novel highly sensitive, rapid and reliable diagnostic tool for enhanced molecular testing for inherited NMDs.
