ATAXIA WITH VITAMIN-E-DEFICIENCY - REFINEMENT OF GENETIC LOCALIZATIONAND ANALYSIS OF LINKAGE DISEQUILIBRIUM BY USING NEW MARKERS IN 14 FAMILIES

Ataxia with vitamin E deficiency (AVED) is an autosomal recessive dise ase characterized clinically by neurological symptoms with often strik ing resemblance to those of Friedreich ataxia. This disorder has been reported previously as familial isolated vitamin E deficiency. We have mapped recently the AVED locus to a 5-cM confidence interval on chrom osome 8q by homozygosity mapping in six Mediterranean families. We hav e now analyzed six new and two previously described families and demon strate genetic homogeneity despite important clinical variability and wide geographic origins. Analysis of nine new tightly linked microsate llite markers, including four characterized in this study, revealed a predominant but not unique mutation in northern African populations, w here this condition is more frequent. Haplotype analysis but also clas sical recombinations allowed us to refine the AVED position to a 1-cM interval. A YAC contig over this interval was constructed from marker STSs and YAC fingerprint data, in order to facilitate the search of th e AVED gene.