LINKAGE ANALYSIS IN BRITISH AND FRENCH FAMILIES WITH IDIOPATHIC TORSION DYSTONIA

Idiopathic torsion dystonia is most commonly caused by an autosomal do minant gene or genes with reduced penetrance. An idiopathic torsion dy stonia locus has been mapped to chromosome 9q34 in one large non-Jewis h and several Jewish kindreds in the USA. Linkage analysis was perform ed in 27 (26 British, one French) small families with idiopathic torsi on dystonia, three of which were Ashkenazi Jewish, using the highly po lymorphic loci argininosuccinate synthetase (ASS) and Abelson oncogene (ABL) which map to 9q34. The cumulative lod score for the more inform ative ASS locus at a recombination fraction of 0.001 was -6.72. A larg e component of this score was derived from three non-Jewish families, indistinguishable clinically from the others, in which individual lod scores excluded a disease locus tightly linked to ASS. Analysis of all the data using HOMOG showed significant heterogeneity, but evidence f or linkage of an idiopathic torsion dystonia gene to 9q34 in a subset of families. The allelic association observed between ASS/ABL and idio pathic torsion dystonia in Ashkenazi families in the USA was also pres ent in British Jewish kindreds. These data suggest genetic heterogenei ty in idiopathic torsion dystonia but indicate the existence of a locu s for idiopathic torsion dystonia at 9q34 in both Jewish and non-Jewis h kindreds in the UK.