[Presymptomatic DNA diagnosis of spinocerebellar ataxia type 1]

Hereditary autosomal dominant ataxias is a clinically and genetically heterogeneous group of diseases characterized by a progressive ataxia combined with the signs of multisystem involvement of the brain and spinal cord. The modern classification of these disorders of the central nervous system is based on recent advances in molecular genetics. In a form of dominant ataxia, spinocerebellar ataxia type 1 (SCA1), the mutation consists of an increased number of copies (expansion) of trinucleotide repeats within the causative gene. This mutational mechanism is characteristic of a group of hereditary neurodegenerative diseases. Revealing this phenomenon provided a tool for direct DNA diagnosis of SCA1 at any stage of the disease, including the preclinical one. This is the first reported case of a direct DNA diagnosis of SCA1 in Russia. The diagnosis was performed in five healthy persons from the risk group, i.e., relatives of patients with a molecularly proven SCA1. Three persons were diagnosed to be presymptomatic carriers of the mutant SCA1 gene; in two persons, the mutation was not found. A complex of moral, ethical, medical, and social problems connected with the application of direct DNA testing of SCA1 in genetic counselling is discussed.