[Autosomal dominant cerebellar ataxias in the Netherlands: a national inventory].

OBJECTIVE

To provide a comprehensive estimate of the number of Dutch autosomal dominant cerebellar ataxias (ADCA) families and patients and thus estimate the minimal prevalence of ADCA in the Netherlands. Furthermore, to observe the relative frequency of SCA mutations and to study genotype-phenotype correlations.

DESIGN

Descriptive study and prevalence computation.

METHODS

Genotyping was based on cytosine-adenine-guanine (CAG)-repeat expansion detection in the SCA1, SCA2, SCA3, SCA6 and SCA7 genes. We analysed the results of SCA mutation analysis with respect to the number of genotyped families, gene carriers, and clinically affected individuals per SCA locus, as well as individual repeat length and age of onset. Parent-offspring couples were studied for anticipation. The minimal prevalence was extrapolated, based on the observation that at least 36% of ADCA families cannot be genotyped.

RESULTS

Per May 1st 2000, 137 Dutch ADCA families were genotyped (SCA1: 15 families; SCA2: 14; SCA3: 64; SCA6: 28; SCA7: 16) and 382 affected individuals had been identified within these families. The extrapolated minimal prevalence was 2.8 per 100,000. All lengths of expanded trinucleotide repeats identified confirmed earlier results regarding pathogenic sizes. Anticipation with an associated increase of repeat length was observed in SCA2 and SCA3 families. The length of the trinucleotide repeat accounted for 65% of the variance in age of onset in SCA3.