FRIEDREICH ATAXIA IN ACADIAN FAMILIES FROM EASTERN CANADA - CLINICAL DIVERSITY WITH CONSERVED HAPLOTYPES

The gene for Friedreich ataxia (FRDA), an autosomal-recessive neurodeg enerative disease, remains elusive, The current candidate region of ab out 150 kb lies between loci FR2 and F8101 near the D9S15/D9S5 linkage group at 9q13-21.1. Linkage homogeneity between classical FRDA and a milder, slowly progressive Acadian variant (FRDA-Acad) has been demons trated, An extended D9S15-D9S5 haplotype (C6) predominates in FRDA-Aca d chromosomes from Louisiana, We studied 10 Acadian families from New Brunswick, Canada, In eight families, affected individuals conformed t o the clinical description of FRDA-Acad; in one, 2 sibs presented with spastic ataxia (SPA-Acad), In the last family, 2 sibs had FRDA-Acad, and one had SPA-Acad, We found that SPA-Acad is linked to the FRDA gen e region, The C6 haplotype and a second major haplotype (B7) were iden tified, The same ataxia-linked haplotypes segregated with both FRDA-Ac ad and SPA-Acad in two unrelated families, The parental origins of the se haplotypes were different, Our observation of different phenotypes associated with the same combination of haplotypes may point to the in fluence of the parent of origin on gene expression, indicate the effec t of modifier genes, or reflect the presence of different mutations on the same haplotype, Our findings underline the need to investigate fa milies with autosomal-recessive ataxias for linkage to the FRDA region , despite lack of key diagnostic manifestations such as cardiomyopathy or absent deep-tendon reflexes. (C) 1996 Wiley-Liss, Inc.