Clinical and laboratory network for LGMD diagnosis, in view of a national registry

The aim of this project is to evaluate the clinical and genetic features of a large group of Italian patients affected with limb girdle muscular dystrophy (LGMD) in view of the creation of a national registry. As this condition is relatively rare, patients will be collected from 8 neuromuscular centres. We plan to make an observational study over a 3 years period defining clinical history among different forms of LGMD and pointing out the most important clinical parameters. These indices could be used in follow-up and to evaluate the efficacy of therapies. We plan to explore the genetic heterogeneity of this group of disorders improving the levels of diagnostic accuracy (with both protein analysis on muscle biopsy as well as genetic testing on DNA) and achieving an efficient and accurate diagnosis of each form. We will investigate for gene dosage with a new dedicated CGH array the autosomal recessive LGMD with mutation identified in a single allele as well as patients with a clear protein defect but without identified mutation in the respective gene. We will select large families and/or suitable autosomal recessive families which will be studied through linkage analysis, homozygosity mapping and direct gene sequencing in order to map new loci and identify new genes. The results of a systematic genetic and observational investigation on LGMDs might be useful to establish a baseline for clinical trials, since new drugs (such as AAV gene transfer, mini-dysferlin, exon-skipping) will be soon available and natural history data as well as accurate genetic diagnosis will be required.