CLINICAL AND GENETIC-ANALYSIS OF A TUNISIAN FAMILY WITH AUTOSOMAL-DOMINANT CEREBELLAR-ATAXIA TYPE-1 LINKED TO THE SCA2 LOCUS

Autosomal dominant cerebellar ataxias (ADCA) type 1 are a clinically a nd genetically heterogeneous group of neurodegenerative disorders. We report a large Tunisian ADCA type 1 family in which 17 patients (mean age at onset +/- SD = 35.6. +/- 15.3 years) were examined. There was m ean anticipation of 10.3 +/- 15.4 years in this family; anticipation w as greater in paternal (28 +/- 8.2 years) than in maternal (2.7 +/- 10 .9 years) transmission. Linkage analysis performed with microsatellite markers linked to the spinal cerebellar ataxia 1 (SCA1) locus on chro mosome 6p and the SCA2 locus on chromosome 12q excluded linkage to SCA 1, but there was close linkage with marker D12S105 (Z(max) = 2.51 at t heta = 0.00). This result was confirmed by multipoint analysis, which generated a maximal lod score of 3.46 at this locus. Multipoint analys is and haplotype reconstruction reduced the interval containing the SC A2 locus to 6.4 cM, a narrowing of the 35-cM interval in a previously described Cuban SCA2 family with a clinical picture similar to that of our family, including a high frequency of postural and action tremor.