Non-association of Friedreich's ataxia and HLA based on five families.

From the Friedreich's Ataxia Research Group and the Departmenl of Immunology, The London Hospital Medical College. Reprints to: Dr. J.A. Sachs, The London Hospital Medical College. Turner Street. London El 2AD. England. Friedreich's ataxia, one of the heredo-familiar spino-cerebellar diseases, is a progressive degenerative disorder always inherited as an autosomal recessive. Its onset is usually before puberty and never after the age of 20 (Geoffrey et al., 1976). The highly polymorphic HLA-A and -B antigenic specificities encoded on chromosome 6 are exceptionally useful for linkage studies within this region. The possibility of finding a genetic marker which could identify susceptible individuals at an early age within a family led to studies on the segregation of HLA in families with autosomal dominant forms of hereditary ataxia in the first instance. Thus, Yakura et al. (1974) showed that in a family with Marie's ataxia the three affected children had inherited the same haplotype from the father, whereas the two unaffected siblings inherited the other paternal haplotype. Information on an extended family with olivopontocerebellar atrophy led Jackson et al. (1971) to suggest that on the basis of linkage estimations (lod scores), there was a strong association between disease susceptibility and HLA. Since ol ivopontocerebel lar atrophy occurs after the age of 20, their study was based only on patients and not on unaffected family members. However, Wastiaux et al. (1977) in another autosomal dominant form of spino-cerebellar atrophy (possibly olivo-pontocerebellar atrophy type 1), found no evidence for linkage with HLA.