Linkage analysis in British and French families with idiopathic torsion dystonia.
Idiopathic torsion dystonia is most commonly caused by an autosomal dominant gene or genes with reduced penetrance. An idiopathic torsion dystonia locus has been mapped to chromosome 9q34 in one large non-Jewish and several Jewish kindreds in the USA. Linkage analysis was performed in 27 (26 British, one French) small families with idiopathic torsion dystonia, three of which were Ashkenazi Jewish, using the highly polymorphic loci argininosuccinate synthetase (ASS) and Abelson oncogene (ABL) which map to 9q34. The cumulative lod score for the more informative ASS locus at a recombination fraction of 0.001 was -6.72. A large 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 for linkage of an idiopathic torsion dystonia gene to 9q34 in a subset of families. The allelic association observed between ASS/ABL and idiopathic torsion dystonia in Ashkenazi families in the USA was also present in British Jewish kindreds. These data suggest genetic heterogeneity in idiopathic torsion dystonia but indicate the existence of a locus for idiopathic torsion dystonia at 9q34 in both Jewish and non-Jewish kindreds in the UK.
Warner
T T
TT
University Department of Clinical Neurology, Institute of Neurology, London, UK.
Fletcher
N A
NA
Davis
M B
MB
Ahmad
F
F
Conway
D
D
Feve
A
A
Rondot
P
P
Marsden
C D
CD
Harding
A E
AE
D001124:Argininosuccinate Synthase / Q000235:genetics; D002874:Chromosome Mapping; D002899:Chromosomes, Human, Pair 9; D004421:Dystonia / Q000235:genetics*; D005006:Ethnicity; D005260:Female; D005602:France; D008040:Genetic Linkage; D006801:Humans; D007585:Jews; D008297:Male; D016374:Oncogene Proteins v-abl / Q000235:genetics; D014102:Torsion Abnormality; D006113:United Kingdom
D016374:Oncogene Proteins v-abl; D001124:Argininosuccinate Synthase