DYT13, a novel primary torsion dystonia locus, maps to chromosome 1p36.13-36.32 in an Italian family with cranial cervical or upper limb onset

Primary torsion dystonia (PTD) is a clinically and genetically heterogeneou s group of movement disorders, usually inherited in an autosomal dominant f ashion with reduced penetrance. The DYT1 gene on chromosome 9q34 is respons ible for most cases of early limb-onset PTD. Two other PTD loci have been m apped to date. The DYT6 locus on chromosome 8 is associated with a mixed ph enotype, whereas the DYT7 locus on chromosome 18p is associated with adult onset focal cervical dystonia Several families have been described in which linkage to the known PTD loci have been excluded. We identified a large It alian PTD family with 11 definitely affected members. Phenotype was charact erized by prominent cranial-cervical and upper limb involvement and mild se verity. A genome-wide search was performed in the family. Linkage analysis and haplotype construction allowed us to identify a novel PTD locus (DYT13) within a 22 cM interval on the short arm of chromosome 1, with a maximum l od score of 3.44 between the disease and marker D1S2667.