ABSTRACT
This chapter explains with the way in which genotype-phenotype correlation in the spinocerebellar ataxias (SCAs) and the study of the molecular characteristics of the pathogenic trinucleotide repeat expansions have led to important advances in the understanding of the mechanisms. The spinocerebellar ataxias are a group of inherited neurological disorders which are clinically and genetically heterogeneous. While expanded pathological alleles may undergo further expansion or contraction during meiosis, it has now been established for many of the disorders that there is a bimodal distribution of normal alleles with a small minority of alleles in the 'high-normal' range. The possibility exists that the changes are merely circumstantial and not directly causative, but perhaps a real effect on cytoplasmic calcium concentration or glutamate neurotransmission is the key step in the pathological process. The only clinical sign that is specific for a single locus is decreased visual acuity leading to blindness due to progressive macular dystrophy in most SCA 7 patients.
