caa a22 4500 445364769 CHVBK 20180317142926.0 cr unu---uuuuu 170323e20110501xx s 000 0 eng 10.1007/s10048-011-0274-9 doi (NATIONALLICENCE)springer-10.1007/s10048-011-0274-9 A high-penetrance form of late-onset torsion dystonia maps to a novel locus (DYT21) on chromosome 2q14.3-q21.3 [Elektronische Daten] [Nina Norgren, Emma Mattson, Lars Forsgren, Monica Holmberg] The primary dystonias are a genetically heterogeneous group of disorders that can be subdivided in pure dystonias, dystonia-plus syndromes, and paroxymal dystonia. Four pure autosomal dominant dystonia loci have been mapped to date, DYT1, 6, 7, and 13, with varying penetrance. We report the mapping of a novel locus for a late-onset form of pure torsion dystonia in a family from northern Sweden. The disease is inherited in an autosomal dominant manner with a penetrance that may be as high as 90%. The torsion dystonia locus in this family was mapped to chromosome 2q14.3-q21.3 using an Illumina linkage panel. We also confirmed the linkage, using ten tightly linked microsatellite markers in the region, giving a maximum LOD score of 5.59 for marker D2S1260. The disease-critical region is 3.6-8.9Mb depending on the disease status of one individual carrying a centromeric recombination. Mutational analysis was performed on 22 genes in the disease-critical region, including all known and hypothetical genes in the smaller, 3.6-Mb region, but no disease-specific mutations were identified. Copy number variation analysis of the region did not reveal any deletions or duplications. In order to increase the chances of finding the disease gene, fine-mapping may be necessary to decrease the region of interest. This report will hopefully result in the identification of additional dystonia families with linkage to the same locus, and thereby, refinement of the disease critical region. Springer-Verlag, 2011 Dystonia nationallicence Late-onset nationallicence Autosomal dominant nationallicence Mapping nationallicence Norgren Nina Unit for Medicine, Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden aut Mattson Emma Department of Genetics and Pathology, Uppsala University, Uppsala, Sweden aut Forsgren Lars Clinical Neuroscience Unit, Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå, Sweden aut Holmberg Monica Medical and Clinical Genetics Unit, Dept. of Medical Biosciences, Umeå University, Umeå, Sweden aut neurogenetics Springer-Verlag 12/2(2011-05-01), 137-143 1364-6745 12:2<137 2011 12 10048 https://doi.org/10.1007/s10048-011-0274-9 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10048-011-0274-9 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Norgren Nina Unit for Medicine, Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden aut NATIONALLICENCE 700 1- Mattson Emma Department of Genetics and Pathology, Uppsala University, Uppsala, Sweden aut NATIONALLICENCE 700 1- Forsgren Lars Clinical Neuroscience Unit, Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå, Sweden aut NATIONALLICENCE 700 1- Holmberg Monica Medical and Clinical Genetics Unit, Dept. of Medical Biosciences, Umeå University, Umeå, Sweden aut NATIONALLICENCE 773 0- neurogenetics Springer-Verlag 12/2(2011-05-01), 137-143 1364-6745 12:2<137 2011 12 10048 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer