Evidence for DYT7 being a common cause of cervical dystonia (torticollis) in Central Europe.

Adult-onset focal idiopathic torsion dystonias (AFITD), such as torticollis, have a prevalence similar to that of multiple sclerosis and usually seem sporadic. Only recently has one large AFITD pedigree "K" with autosomal dominant inheritance and reduced penetrance from Northwest Germany provided the opportunity to identify a gene locus on chromosome 18p. We have now tested the relevance of this DYT7 gene locus in a collective of 18 nuclear AFITD families from Central Europe who were genotyped with chromosome 18p microsatellites. In three families, the affected relatives did not share a chromosome 18p haplotype, suggesting locus heterogeneity in AFITD. In the remaining 15 families, significant allelic association was observed for marker D18S1098. This result suggests that DYT7 is a common cause for AFITD at least in Central Europe, that many patients are descended from a common ancestor, and that the DYT7 gene is mapped in a 4.4 centimorgan subregion of chromosome 18p.

Sporadic focal dystonia in northwest Germany: molecular basis on chromosome 18p.

Idiopathic focal dystonia (IFD) is the most common form of idiopathic torsion dystonia in the Euroamerican population, with a prevalence of about 30 per 100,000. Although most patients claim a negative family history, we recently mapped this syndrome to chromosome 18p as an autosomal dominant trait in Family K from Northwest Germany. We now have investigated sporadic patients with IFD from the same geographic area both clinically and molecularly with chromosome 18p markers. The data indicate that most of these apparently sporadic patients have inherited the same mutation as Family K from a common ancestor and, in fact, owe their disease to autosomal dominant inheritance at low penetrance. The data also indicate that this dystonia mutation (DYT7) is the predominant cause of IFD, at least in this area of Northwest Germany, and that its location can be narrowed from a 30- to a 6-centimorgan region close to marker D18S1098.