Molecular genetic and clinical study in 20 families of Autosomal Dominant Ccrebcllar Ataxia (ADCA) and in 20 sporadic cases

The dominant cerebellar ataxias (ADCAs) represent a clinically and genetically heterogeneous group of disorders. Recently the SCA2 and SCA6 genes have been cloned and the mutation consisted of an expansion of an unstable CAG repeat, likely previously demonstrated for SCA1. SCA3/MJD and DRPLA. Patients of 20 Italian kindreds affected by ADCA and 20 sporadic cases of progressive cerebellar ataxia were screened for SCA1, SCA2. SCA3/MJD and SCA6 mutations. The SCA1 and SCA2 mutations represented respectively 15% and 30% of our families of ADCAI. The SCA3/MJD mutation wasn't identified in any family; the SCA1, SCA2, SCA3/MJD mutations were demonstrated in none of sporadic cases. In SCA1 and SCA2 families the anticipation phenomenon was present; it was observed in our SCA2 families only in paternal transmission, with a mean anticipation in age at onset of 13 years. Both SCA1 and SCA2 families demonstrated a clinical heterogenity, with a large spectrum of clinical features. In our SCA2 patients the more frequent clinical features were represented by ophthalmoparesis. slow saccades, ipo-areflexia and electrophysiological signs of neuropathy.