• Telethon Exploratory Project – Call 2012
  • Identification of the gene responsible for a new form of distal myopathy

Distal myopathies are a heterogeneous group of genetic disorders clinically characterized by progressive muscular weakness of upper and lower limbs. More than 20 different forms have been classified based on clinical and genetic studies and for 14 of them the causative gene has been identified.

This complicates molecular testing limiting the possibility of a reliable molecular diagnosis especially for those forms with still unknown molecular basis.

The aim of this project is to identify the gene responsible for a new autosomal dominant form of distal myopathy characterized by a predominant involvement of hand muscles. This form has been characterized in a multigenerational Italian family for which all known genetic causes of distal myopathy have been excluded. In addition, SNP-array based whole genome analysis led to the identification of three chromosomal regions co-segregating with the disease with a total length of 9 Mb. Overall, these data support the existence of a new disease gene associated to this form of distal myopathy.

In order to achieve the final objective we plan to use an approach that combines positional cloning information and next generation high-throughput sequencing. The three regions linked to the disease will be fully sequenced and pathogenic mutations identified through an already optimized analytical pipeline for high confidence variant calling, annotation and prioritization. Further validation will be achieved by assessing the correct segregation of the mutation within the family, by excluding its presence in a large ethnically matched control sample and by searching for new mutations in independent patients.

Considering the wide genetic heterogeneity of distal myopathies (more than 20 loci), the expected results would enhance the quality of genetic counseling services associated with genetic testing and would improve the clinical management of patients avoiding erroneous diagnosis.

Principal Investigator


MeSH terms Distal Myopathies, genetic linkage, High-Throughput Nucleotide Sequencing, Genetic Testing