![]() 4 Dystonia is not always a prominent feature of these conditions. However, in these disorders, the movement disorder is quite varied and reflects various combinations of dystonia, chorea, ataxia, and sometimes other abnormalities. Similarly, the paroxysmal dyskinesias were assigned to DYT8 ( MR-1), DYT10 or DYT19 ( PRRT2), and DYT9 or DYT18 ( SLC2A1). Sometimes there is myoclonus without any dystonia, and the disorder is then called essential myoclonus. However, dystonia is often quite subtle, with a slight tilting of the head, or slightly scalloped posture of a hand. 2, 3 Many patients with this disorder also have dystonia, and dystonia may sometimes be severe. However, the most consistent feature of this disorder is myoclonus, not dystonia. For example, the myoclonus–dystonia syndrome was assigned to the DYT11 locus, and at least one causative gene has been identified ( SGCE). ![]() The DYT prefix was intended for disorders where dystonia is an important aspect of the phenotype. 1 The problems are illustrated here using dystonia as an example, although similar problems have been described for other movement disorders. This simple nomenclature system has been in use for many years, but it has also led to numerous problems. Prefix assignments were never generated for certain disorders where linkage studies had not yet identified meaningful targets, including tremor, myoclonus, paroxysmal dyskinesias, and others. In this way, multiple unrelated families that might share defects in the same gene could be identified and analyzed together to improve the chances of finding the relevant gene. When linkage studies for a new family pointed to a novel locus different from previously identified loci, the prefix was appended with a distinct number (e.g., DYT1, DYT2, DYT3, etc.). Movement disorders were grouped according to the main aspects of the clinical phenotype and given a specific prefix such as Parkinson’s disease (PARK), spinocerebellar ataxia (SCA), hereditary spastic paraplegia (HSP), or dystonia (DYT). The HUGO convention was applied for naming loci for candidate genes to all human disorders. ![]() Therefore, the original intention of the HUGO locus nomenclature system was to provide a temporary label to aid in the identification of families for linkage analyses. To aid the process of identifying families with similar disorders, the Human Genome Organization (HUGO) developed a convention for acknowledging potential new genes for families in which linkage studies pointed to a specific chromosomal location or “locus.” HUGO intended that the locus name should be dropped after the gene was discovered because knowing the gene is more important than linkage-based statistical estimates of its location in the genome. Therefore, identifying multiple unrelated families with the same condition was historically essential for the identification of novel disease genes. Having multiple large and unrelated families greatly aided this process by increasing the statistical power to detect correlations between the disease phenotype and the genetic marker. Then, large stretches of DNA were sequenced in the chromosomal locations closest to the markers that correlated best with the disease phenotype. Historically, most disease-associated genes were discovered by a process known as “linkage analysis.” In brief, large families with multiple individuals affected by a specific disorder were collected, and genetic “markers” with known locations spread across all chromosomes were examined for family members with and without the disorder.
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