Clinical Genetics and Epidemiology

The group has been active since 2005. Our research was originally focused on mitochondrial diseases and later expanded to include a whole series of other genetic disorders.

Currently the group has two main lines of research. The first concerns the biogenesis of the mitochondrial respiratory chain, and in particular of Coenzyme Q and disorders of intermediate metabolism. Our goals are to identify and characterize human genes involved in the biogenesis of the mitochondrial respiratory chain, identify mutations in patients with these diseases, to develop simple models to characterize these mutations, to study their pathophysiology, and test new therapeutic approaches. In recent years we have expanded our scope of research to include other types of metabolic diseases, as well as genetic disorders unrelated to cellular metabolism.

The second field of research concerns genetic diseases in general. The expansion of our diagnostic service has provided us with an incredible amount of genetic data (we have analyzed more than 10,000 patients with NGS, for a variety of different conditions). The main limitation of this approach is that it is often very difficult to establish the pathogenicity of variants identified by diagnostic tests. In recent years, we have developed several models (hybrid minigenes, yeast, CRISPR-CAS9-edited human cells, and the nematode C. elegans) that have allowed us to validate many new variants and establish genotype-phenotypic correlates for several diseases and to identify new genes associated with human diseases.

The main results obtained in the last year are the identification of a specific role for frataxin, the deficient protein in Friedreich’s Ataxia, in the biogenesis of complex I of the respiratory chain, and the identification of the oxidative decarboxylase that catalyzes the first step of the biosynthesis of coenzyme Q ring, an enzyme that has eluded researchers for over 30 years.