Molecular and clinical correlations in spinocerebellar ataxia 2: a study of 32 families

Spinocerebellar ataxia 2 (SCA2) is caused by the expansion of an unstableCAG repeat encoding a polyglutamine tract. One hundred and eighty fourindex patients with autosomal dominant cerebellar ataxia type I werescreened for this mutation. We found expansion in 109 patients from 30families of different geographical origins (15%) and in two isolated caseswith no known family histories (2%). The SCA2 chromosomes contained from 34to 57 repeats and consisted of a pure stretch of CAG, whereas all testednormal chromosomes (14-31 repeats), except one with 14 repeats, wereinterrupted by 1-3 repeats of CAA. As in other diseases caused by unstablemutations, a strong negative correlation was observed between the age atonset and the size of the CAG repeat (r = -0.81). The frequency of severalclinical signs such as myoclonus, dystonia and myokymia increased with thenumber of CAG repeats whereas the frequency of others was related todisease duration. The CAG repeat was highly unstable during transmissionwith variations ranging from -8 to +12, and a mean increase of +2.2, butthere was no significant difference according to the parental sex. Thisinstability was confirmed by the high degree of gonadal mosaicism observedin sperm DNA of one patient.