title: Clinical and genetic analysis of a Tunisian family with autosomal dominant cerebellar ataxia type 1 linked to the SCA2 locus.
abstract: Autosomal dominant cerebellar ataxias (ADCA) type 1 are a clinically and 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 mean anticipation of 10.3 +/- 15.4 years in this family; anticipation was 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 chromosome 6p and the SCA2 locus on chromosome 12q excluded linkage to SCA1, but there was close linkage with marker D12S105 (Zmax = 2.51 at theta = 0.00). This result was confirmed by multipoint analysis, which generated a maximal lod score of 3.46 at this locus. Multipoint analysis and haplotype reconstruction reduced the interval containing the SCA2 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.
authors.affiliation: Institut National de Neurologie, Tunis, Tunisia.
authors.forename: S
authors.initials: S
authors.lastname: Belal
authors.forename: G
authors.initials: G
authors.lastname: Cancel
authors.forename: G
authors.initials: G
authors.lastname: Stevanin
authors.forename: F
authors.initials: F
authors.lastname: Hentati
authors.forename: C
authors.initials: C
authors.lastname: Khati
authors.forename: C
authors.initials: C
authors.lastname: Ben Hamida
authors.forename: G
authors.initials: G
authors.lastname: Auburger
authors.forename: Y
authors.initials: Y
authors.lastname: Agid
authors.forename: M
authors.initials: M
authors.lastname: Ben Hamida
authors.forename: A
authors.initials: A
authors.lastname: Brice
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002874:Chromosome Mapping; D005260:Female; D008040:Genetic Linkage; D005819:Genetic Markers; D006801:Humans; D008126:Lod Score; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D016133:Polymerase Chain Reaction; D013132:Spinocerebellar Degenerations / Q000235:genetics*; D014416:Tunisia
chemical_list: D005819:Genetic Markers