Identified the genetic defect responsible for a particular genetic form of ataxia, SCA28: to announce a study financed by Telethon and published online on the site Nature Genetics Franco Taroni, researcher of Neurologico Carlo Besta “in Milan, Marco Muzi-Falconi University of Milan and colleagues. The term ataxia is derived from the greek “disorder” and indicates a disorder of motor coordination that is often also associated with incontinence, difficulty swallowing and involuntary movements of limbs, trunk, head, eyes. The portion of the brain affected is the cerebellum, the control station of all voluntary movements of our body. Often the result of infection, poisoning or radiation, the ataxia may also have a genetic basis. In these cases we speak of genuine hereditary ataxias is estimated that in Italy about 5000 people are affected, both with onset in childhood or in adulthood, but always with a progressive course. Even if it occurs essentially with the same symptoms, hereditary ataxias are very heterogeneous with regard to the genetic defect responsible (and, consequently, also for the method of transmission from one generation to another). The SCA28 is a new form of the disease: diagnosed for the first time in the world group of Franco Taroni in an Italian family, is transmitted as an autosomal dominant, that is enough to inherit a copy of the altered gene from one parent (in turn affected ) to manifest the disease. By studying the DNA of some patients without an accurate diagnosis (a condition that currently covers half of people with hereditary ataxia), researchers in Milan have managed to locate the gene at first, then to accurately identify and define the specific abnormalities responsible for disease. The gene in question is called AFG3L2 and contains information for a protein involved in the metabolism of mitochondria, the power plants of our cells. Its role is to cut and break down other proteins, sometimes to bring them up and running, in other cases to start the disposal if no longer useful for the cell. A peculiarity of AFG3L2 is because of its close association with another protein, paraplegin in turn associated with another neurodegenerative disease of genetic origin, hereditary spastic paraplegia. Despite the two proteins are in fact the wheels of the same machine, are associated with two very different diseases. Furthermore, researchers have demonstrated how the structure of AFG3L2 and paraplegin is conserved at the level of evolution: just think that even species that are very distant from man as yeast or certain bacteria that live only at high temperatures possess a cellular machinery very similar. It is using a yeast that the team coordinated by Franco Taroni and Marco Muzi-Falconi was able to identify the mechanism that is wrong in patients with SCA28.

The group’s work has an impact immediately in the diagnostic field, particularly important in the case of diseases such heterogeneous in terms of how the genetic defect responsible for ataxia. Looking ahead, however, the next step for researchers will increase knowledge on the mechanism of SCA28 and see if it can actually be included in the promising field of research of mitochondrial diseases.

Source:lescienze.espresso.repubblica.it