Spinocerebellar ataxia type 7 (SCA7) - correlations between phenotype and genotype in one large Belgian family

Spinocerebellar ataxia type 7 (SCA7), in which the degenerative process als o affect the retina, belongs to the category of the autosomal dominant cere bellar ataxia type II (ADCA II). We have described the neuropathology of th is condition [Martin JJ, Van Regemorter N, Krols L, Brucher JM, de Barsy T, Szliwowski H, et al. On an autosomal dominant form of retino-cerebellar de generation: an autopsy study of five patients in one family. Acta Neuropath ol (Berl) 1994;88:277-286] in a very large Belgian family (CA-1). We have o bserved anticipation in the age of onset with increasing severity of the sy mptoms in consecutive generations. The SCA7 gene was mapped to chromosome 3 p12-13 [David G, Abbas N, Stevanin G, Durr A, Yvert G, Cancel G, et al. Clo ning of the SCA7 gene reveals a highly unstable CAG repeat expansion. Nat G enet 1997;17:65-70; Del-Favero J, Krols L, Michalik A, Theuns J, Lofgren A, Goossens D, et al. Molecular genetic analysis of autosomal dominant cerebe llar ataxia with retinal degeneration (ADCA type II) caused by CAG triplet repeat expansion. Hum Mol Genet 1998;7:177-186], and the gene identified. S CA7 is a new gene of unknown function that contains an expansion of CAG rep eats in SCA7 patients. During the procedure of positional cloning, we exami ned 26 patients belonging to the CA-1 family and realized, in some of them, an ophthalmologic examination and neuro-imaging of the brain. This allowed us to differentiate four groups: (1) asymptomatic young carriers with 38 t o 43 CAG repeats; (2) mildly symptomatic, older patients with 38-41 CAG rep eats; (3) patients with the full-blown picture of SCA7 and age of onset dur ing adolescence, with 54-55 CAG repeats; (4) children with early onset and rapid fatal course of the disease who had over 55 CAG repeats. We were able to draw correlations between clinical phenotype, age at onset and CAG repe at number and to make predictions, ro some extent, as to the clinical cours e of the disease in new patients. (C) 1999 Elsevier Science B.V. All rights reserved.