AUTOSOMAL-DOMINANT CEREBELLAR-ATAXIA TYPE-I - CLINICAL AND MOLECULAR STUDY IN 36 ITALIAN FAMILIES INCLUDING A COMPARISON BETWEEN SCA1 AND SCA2 PHENOTYPES

We studied 83 patients from 36 Italian families with autosomal dominan t cerebellar ataxia type I. Mean onset age +/- SD was 34.2 +/- 12.8 ye ars with a mean anticipation of 12.8 +/- 15.1 in 52 parent-offspring p airs. Onset age anticipation occurred predominantly through paternal t ransmission. Mean age at death was at 56.5 +/- 15.5 years. The most co mmon associated features were supranuclear ophthalmoplegia, corticospi nal signs, peripheral neuropathy and cognitive impairment. Cerebellar atrophy was constant at MRI and usually associated with shrinkage of t he pens and degeneration of the pontine transverse fibres. Direct muta tion analysis in 29 families showed two families with SCA1 and none wi th Machado-Joseph/SCA3 mutation. We performed linkage analysis in the ten largest families. Two of them showed linkage to SCA2 locus and non e to SCA4 and SCA5 loci. SCA2 patients showed higher occurrence of per ipheral neuropathy and slow saccades, rarer corticospinal signs and a milder course of the disease in comparison with SCA1 patients.