LOCALIZATION OF AUTOSOMAL-DOMINANT CEREBELLAR-ATAXIA ASSOCIATED WITH RETINAL DEGENERATION AND ANTICIPATION TO CHROMOSOME 3P12-P21.1

We present linkage analysis on a large Swedish five-generation family of 15 affected individuals with autosomal dominant cerebellar ataxia ( ADCA) associated with retinal degeneration and anticipation, Common cl inical signs in this family include ataxia, dysarthria and severely im paired vision with the phenotype ADCA type II, Different subtypes of A DCA have proven difficult to classify clinically due to extensive phen otypic variability within and between families. Genetic analysis of a number of ADCA type I families shows that heterogeneity exists also ge netically, During the last few years several types of ADCA type I have been localized and to date six genetically distinct forms have been i dentified including SCA1 (6p), SCA2 (12q), SCA3 and Machado-Joseph dis ease (MJD) (14q), SCA4 (16q), and finally SCA5 (11), We performed a ge nome-wide search of the Swedish ADCA type II family using a total of 2 70 microsatellite markers, Positive lod scores were obtained with a nu mber of microsatellite markers located on chromosome 3p12-p21.1. Three markers gave lod scores over 3 with a maximum lod score of 4.53 achie ved with the marker D3S1600. The ADCA type II gene could be restricted to a region of 32 cM by the markers D3S1547 and D3S1274.