Cerebellar ataxia and total albinism: A kindred suggesting pleiotropism or linkage

Abstract

In a sibship occurring in a kindred with a high degree of inbreeding, four persons with an auto‐somal recessive type of cerebellar ataxia all had total albinism (tyrosinase‐negative, as judged from investigation of the prohand). Of the five healthy sibs, all had normal pigmentation. Relatively close genetic linkage between the loci for total albinism and this variant of cerebellar ataxia appears to be a more likely interpretation of the observed distribution than is the possibility of a pleiotropic effect of one mutant gene. However, the linkage scores for this sibship are not sufficiently high to formally prove the existence of linkage, the lod score for a recombination fraction of 0 being 2.4. The case for linkage is not significantly weakened if it is postulated that the phenotype of a paternal aunt who has total albinism hut no neurological disorder reflects one recombinant event, but absolute linkage would then be excluded. It is necessary to consider the possibility of close linkage, whenever concurrence of otherwise. distinct genetic disorders is observed in one or in a very low number of families, suggesting a “new syndrome”. If the observation in the pedigree studied reflects true linkage between total albinism and cerebellar ataxia, linkage studies with respect to hemoglobin variants are called for in families where these anomalies occur, since non‐α‐hemoglobin loci are linked to albinism in certain other species and there is good reason to believe that there has been a high degree of conservatism in chromosomal evolution.