IDENTIFICATION OF THE GENE RESPONSIBLE FOR A NOVEL FORM OF AUTOSOMAL DOMINANT SPINOCEREBELLAR ATAXIA

The term ataxia refers to poor coordination of movement and is often used to describe uncoordinated, unsteady gait. Hereditary forms of ataxia are a group of genetic disorders producing a slowly progressive loss of gait coordination and are often associated with poor coordination of hand and eye movement, and speech. Genetic forms, which must be carefully distinguished from acquired causes of ataxia, can be autosomal dominant (such as Spinocerebellar ataxias or SCA) or autosomal recessive (Friedreichs ataxia, Ataxia Telangiectasia). Twenty-one major types of autosomal dominant hereditary SCAs have now been mapped, and among these eleven genes were discovered. In collaboration with the Department of Biochemistry and Genetics of the Neurological Institute “C. Besta”- Milan, we have collected an Italian family with a new form of spinocerebellar ataxia associated with oculomotor abnormalities. We excluded the possible involvement of all known SCA genes (SCA1-3, 6-8, 10, 12, e 17), and all known loci (SCA4, 5, 11, 13-16, 18, 19, 21), proving that the responsible gene is still not known.Statistical modeling allows to predict that a procedure known as “genome-wide screen”, will be able to detect the disease locus in this family. The Human Genome Project facilities will provide us a list of genes in the region, that will be screened to search for the one that mutated is responsible of this disease The identification of a new SCA gene would be of great benefit for pre- and post-natal molecular diagnosis in this family and may be of relevance among other familial SCAs. It will be also important to understand the disease mechanisms of ataxia, and may be of value in understanding other more common neurodegenerative diseases, such as Alzheimer and Parkinson.