Muscular dystrophies are rare inherited disorders of skeletal muscle with reduced ability to generate force, and often with severe disability and decreased life expectancy. Dystrophies form a clinically and genetically heterogeneous group. Since the discovery of the dystrophin protein involved in Duchenne/Becker muscular dystrophy (DMD/BMD), several other protein dysfunctions have been described in the dystrophin related glycoprotein complex of the sarcolemma. The disruption of the a,b,g,d sarcoglycans, , calpain, caveolin-3, dysferlin, laminin-2, merosin, fukutin-related protein and others are responsible for the different types of limb-girdle muscular dystrophies (LGMDs), Emery-Dreifuss, congenital muscular dystrophies and other disorders. In the last few years, we introduced in our laboratory the genetic analysis of several such diseases to provide exact diagnosis for the affected patients.

For the analysis of Duchenne/Becker muscular dystrophy (DMD/BMD), to supplement the multiplex PCR detection of the most common dystrophin gene deletions, cDNA probes were introduced in order to detect carrier status and to delimit exact deletion borders. In addition, the new multiplex ligation-dependent probe amplification (MLPA) technique was introduced that enabled the examination of the entire dystrophin gene with highlights on specific point mutations, exact analysis of the deletions and duplications and moreover, on efficient screening of the carrier status. During the last years, 141 affected persons were screened and 77 had deletions whereas out of the 86 female relatives 39 proved to be carrier of the mutations.

Another severe and relatively frequent disorder, the facioscapulohumeral muscular dystrophy (FSHD) is caused by the deletions of D4Z4 repetitive sequences in 4q35 region. These deletions are detected by Southern blot analysis using the p13E-11 probe in our laboratory. Epigenetic influences may play a crucial role in modulating phenotype. Altered transcriptional activities of genes proximal to the D4Z4 sequences have a key role in the pathomechanism. Therefore, this effect was studied by methylation analysis in addition to the diagnostic procedure. For the confirmation of the clinical diagnosis 77 patients were genetically analyzed and 51 positive cases were detected, whereas out of the 43 asymptomatic family members 5 carried the FSHD mutation.

The differential diagnosis of the heterogeneous LGMD group requires first the specific analysis of the dystrophin-associated glycoproteins. Muscle biopsies and blood samples of 122 patients were sent to the Friedrich-Baur-Institute in Munich; in total 56 immunohistochemical and 20 Western blot analyses have been performed. In 26 patients the exact pathogenic mutation has been identified by DNA sequencing.

To summarize, we have established an efficient way in the diagnostic procedure of different muscular dystrophies with the collaboration of the University of Munich. Several new LGMD mutations have been identified, thus enabling a precise genetic diagnosis of the muscular dystrophy of the patient. In the case of DMD/BMD, novel deletions have been found and carrier detection in female relatives was improved enormously. In FSHD disease, translocation cases and epigenetic factors have been detected, which might help to understand the pathomechanism and geno- and phenotype correlations. All these achievements help us to provide a better genetic service for the patients and to give proper genetic counseling, including the possibility of prenatal analyses, for the affected families.