FRIEDREICH ATAXIA PHENOTYPE NOT LINKED TO CHROMOSOME-9 AND ASSOCIATEDWITH SELECTIVE AUTOSOMAL RECESSIVE VITAMIN-E-DEFICIENCY IN 2 INBRED TUNISIAN FAMILIES

Friedreich's ataxia (FA) is an autosomal recessive neurodegenerative d isorder, the disease locus (FRDA) of which has been assigned to 9q13-q 21.1 by genetic linkage analysis in affected families. We report two l arge inbred Tunisian families with FA manifestations that did not show the expected linkage. The disease locus could be excluded from a larg e (12 cMo) region around FRDA. This is the first report providing evid ence for nonallelic genetic heterogeneity for the FA clinical phenotyp e. On subsequent analysis, all patients had very low levels of serum v itamin E whereas the parents and healthy sibs had normal vitamin E lev els. This establishes that the selective vitamin E deficiency with nor mal fat absorption is an autosomal recessive trait, which is associate d in the two families reported here with the FA phenotype.